Parathyroid Surgical Anatomy Notes

Parathyroid And Adrenals

Describe the applied anatomy of parathyroid.

Parathyroid Gland Surgical Anatomy

• These are the endocrinal glands situated in the neck and secrete the hormone parathormone (PTH). Their secretion is not dependent on pituitary gland.
• They are 4 in number; 2 on the right and 2 on the left.

Read And Learn More: General Surgery Notes

• Superior parathyroids are derived from endoderm of 4th branchial arch and thus, they develop along with the thyroid gland. Superior parathyroids are found in relation to inferior thyroid artery in the middle of posterior aspect of thyroid gland.
• They are situated in the fat above inferior thyroid artery, close to cricothyroid artery and cricothyroid articulation. They are constant in position. They are smaller (30–40 mg). They are dorsal to recurrent laryngeal nerve (RLN).
• Inferior parathyroids develop from endoderm of 3rd branchial arch (with thymus) and are not constant in position.
• They may be seen in the lower pole, within fascial sheath of thyroid gland, low down in the neck (rarely in the mediastinum), outside the fascial sheath or even within thyroid gland. They are large (30 to 50 mg). They are ventral to RLN.

• Parathyroids appear golden-yellow to light brown in adults. In children, they are pinkish in colour.

Parathyroid Blood Supply:

Inferior thyroid artery supplies both the parathyroids in about 95% of cases by a leash of vessels. Ligature of both inferior thyroid arteries may not result in hypoparathyroidism because there is adequate collateral circulation and a few branches of superior thyroid artery also supply 20% of upper glands.

Parathyroid Glands

Parathyroid Histology:

Principal cells (chief cells) are the cells which secrete PTH (parathormone). Water clear cells (rich in glycogen) are found in hyperplastic and neoplastic glands.

Congenital Anomaly And Syndrome

DiGeorge syndrome: Congenital absence of the parathyroid glands and thymus. Neonatal hypoparathyroidism along with absence of thymus-dependent lymphoid system.

Physiology—Calcium And Action Of Pth And Calcitonin

1. PTH is a peptide containing 84 amino acids. It is secreted in response to increase in calcium or decrease in magnesium. Actions of PTH are:
2. Resorption and mobilisation of calcium from the bone.
3. Increased reabsorption of calcium from kidney prompting excretion of phosphate.
4. Enhances absorption of calcium from the gut.

• Thus, PTH increases serum calcium level.
• Normal serum calcium level 9–11 mg/dl (total).
• In normal persons, the PTH is balanced by calcitonin, secreted from C cells of the thyroid glands.

Calcium:

• Most abundant cation in human beings
• 50% of calcium is in the ionised form, which can be measured
• 50% of calcium is bound to albumin. Hence, total calcium levels will be low when albumin levels are low
• Total calcium levels: 9–11 mg/dl
• Calcium is absorbed in the small intestines
• Sources of calcium: Milk, yoghurt and cheese, green peas, beans, oranges. Daily requirement: 1000–1300 mg/ day
• Calcium is an important ion for blood coagulation, cellular activity, bone density and neuromuscular activity

Calcitonin

• It is released from ‘C’ cells—parafollicular cells of the thyroid gland.
• Normal values are unmeasurable less than 10 pg/ml.
• It reduces calcium levels by inhibiting activity of osteoclasts. Thus its action is opposite that of PTH.
• It also increases excretion of calcium in the urine.
• Describe and discuss the clinical features of hypo- and hyperparathyroidism and the principles of their management.

Tetany

Tetany is a condition wherein there is hyperexcitability of peripheral nerves.

Causes of Tetany:

1. Hypoparathyroidism: It results from surgical removal of parathyroids. Subtotal thyroidectomy and near-total thyroidectomy are the most common causes of tetany.
2. Hypoparathyroidism may be ‘familial’ variety or neonatal variety. It may be temporary after thyroidectomy or permanent, if all the 4 parathyroids are removed or deprived of their blood supply. The incidence is around 1–2%.
3. Severe respiratory alkalosis can cause tetany as in hyperventilation.
4. Low calcium levels can occur due to dietary factors or poor absorption from the gut or acute pancreatitis, chronic renal failure, etc.
5. Osteomalacia and rickets due to deficiency of vitamin D.
6. Hypokalaemic alkalosis of pyloric stenosis.
7. Following massive transfusion (citrate overload).

Tetany Signs And Symptoms:

Tetany—Clinical Features:

• Creaking or grating sound (stridor)
• Circumoral pallor
• Carpopedal spasm—Trousseau’s sign
• Chovstek’s sign
• Clonic seizure
• Convulsions (rare)

Observe 6 ‘Cs’

1. Tingling and numbness of the fingers, toes, lips (circumoral paraesthesia) and occasionally, with circumoral pallor.
2. Cramps of the hands and feet.
3. In severe hypocalcaemia, there may be carpopedal spasm. Metacarpophalangeal (MP) joints are flexed, interphalangeal joints are extended and the thumb is adducted. This is called thumb in palm deformity (obstetrician’s hand). In the foot, extension in the ankle joints and flexion of the toes are seen.

4. Stridor is a dangerous complication of severe tetany due to spasm of muscles of respiration.

5. Latent tetany can be diagnosed by:

• Tapping the facial nerve at the angle of jaw. This produces twitching of eyelids, corner of the mouth, etc. It is called Chvostek’s sign. It indicates facial nerve hyperexcitability.
• Trousseau’s sign: When a blood pressure cuff applied to the arm is inflated above the systolic pressure (200 mm of Hg), the hands and feet go into spasm (obstetrician’s hand, carpopedal spasm).

6. Spasm of intraocular muscles results in blurring of vision.

7. Convulsions, even though rare, can occur in infants. Diagnosis

This is established by estimating serum calcium level which is usually <7 mg%.

Parathyroid Glands

Tetany Treatment:

1. Oral calcium such as calcium lactate, calcium gluconate may relieve mild symptoms.
2. In acute cases, injection calcium gluconate 10% (10 ml) should be given slowly intravenously over 10 minutes to avoid cardiac arrhythmias.
3. If any precipitating cause is detected, it needs to be corrected.

Hyperparathyroidism (Hpt)

Hyperparathyroidism is an uncommon disease and occurs due to an increased activity of parathyroids and manifests as hypercalcaemia.

Types of Hyperparathyroidism:

• Primary hyperparathyroidism: It refers to hyperactivity of parathyroids due to an adenoma or primary hyperplasia of parathyroid glands.
• Secondary hyperparathyroidism: It occurs due to persistently low levels of calcium as in chronic renal failure and malabsorption, which results in decreased levels of calcium and increased levels of hyperphosphataemia.
• Tertiary hyperparathyroidism: This is seen in patients who undergo dialysis and transplantation for chronic renal failure. After a few years of prolonged stimulation, autonomy develops and the secondary hyperparathyroidism changes into tertiary hyperparathyroidism. They can also have problems similar to primary hyperparathyroidism.

Primary Hyperparathyroidism

Hyperparathyroidism Incidence:

0.50 to 1 per 1000 population in United States. More common in postmenopausal women.

Hyperparathyroidism Aetiology:

Exact cause of primary hyperparathyroidism (PHPT) is unknown.

1. Familial/genetic: Can be a part of MEN syndrome I and MENII A or familial PHPT with jaw tumour syndrome. Both occur due to genetic mutation.
2. Low dose therapeutic ionising radiation is also one of the causes.
3. Lithium is associated with parathyroid hyperplasia and primary HPT. Interestingly there is no hypercalciuria and bone mineral density is not affected.
4. Renal leak of calcium and declining renal function with age may also be causative factors for primary HPT.

Hyperparathyroidism Pathology: 

• Single chief cell adenoma is the most common cause (80%). It can be due to diffuse hyperplasia involving all 4 glands (5–10% of cases).
• Very rarely, it can be due to carcinoma arising in the parathyroid glands (1%).
• Adenoma can be a part of multiple endocrine neoplasia (MEN) syndrome.

Hyperparathyroidism Clinical Features:

• Common in females: Female to male ratio is 4:1.
• Age: 30–60 years, the most common age group is 5th decade—middle aged
• Incidence is 1:1000 patients.

Pathology:

• • Adenoma—reddish brown, only 1 gland is enlarged
  • Chief cell hyperplasia—reddish brown, 1 gland is enlarged
  • Water cell hyperplasia—chocolate brown, 1 gland is enlarged
  • Multiple gland enlargement is a feature of familial disease
• The most common presentation is asymptomatic hypercalcaemia in about 50% of the patients and renal stones in 25% of the patients. The clinical features are as follows.

1. Bone Disease—Painful Bones:

• Due to increasing levels of PTH, extensive skeletal decalcification occurs. This results in bony pains, pathological fractures due to brittle bones, subperiosteal erosions, cysts in the phalanges, mandible, skull, etc.
• They are called pseudotumours. The changes are similar to that seen in osteitis fibrosa cystica (von Recklinghausen’s disease).
• Thus, osteopenia, osteoporosis and osteitis fibrosa cystica are found in 15% of PHPT.

2. Renal Disease—Renal Stones:

• Increased calcium levels result from increased calcium absorption from the kidneys. Hence, patients are prone to develop renal stone and nephrocalcinosis (calcification of kidney), hypertension.
• Calcium also increases the tone of the vessels which adds to the hypertension. Primary hyperparathyroidism is the cause of stones in 1–3% of all patients with kidney stones and in 10% of those who have recurrence of stones.
• Calculi are specially composed of calcium phosphate or oxalate.

3. Abdominal Groans:

• Calcium stimulates gastrin which is a powerful stimulator of acid. This may result in pain abdomen due to peptic ulcer. The patient can present with dyspeptic symptoms.
• Calcium can cause pancreatitis, resulting in pain radiating to the back.
• Metastatic calcification is also a feature.
• Increased incidence of gallstones has been reported as a consequence of increase in secretion of calcium in the bile-calcium bilirubinate stone.
• All these factors result in abdominal pain, which has been called abdominal groans.

4. Psychiatric Moans:

• Hypercalcaemia can result in depression, fatigue, anxiety, psychosis and even coma.
• These patients, more often women, mostly middle age, having bony pains, backaches and behavioural abnormalities are thought to have a psychiatric illness.
• They are referred to mental institutions, orthopaedic department, gynaecology department and are shunted from doctor to doctor.

5. Fatigue Overtones:

Many patients present with weakness and fatigue.

Acute Presentation of Hypercalcaemia:

• Abdominal pain
• Oliguria
• Dehydration
• Vomiting
• Coma

Hypercalcaemia Symptoms:

• Asymptomatic 50–60% of cases
• Renal stones 25–30%
• Bone disease 8–10%
• Joint pains 3–5%
• Abdominal pain (peptic ulcer) 3–5%
• Hypertension 3–5%

Hypercalcaemia Other Features:

• Corneal calcification/band keratopathy (inside iris) may be seen in the eye on slit-lamp examination.
• Proximal myopathy, muscle wasting is also seen.
• Interestingly, clinical examination of the neck may not reveal any parathyroid enlargement. Hence, the diagnosis should be suspected by the various symptoms.
• High index of suspicion is necessary in arriving at a proper diagnosis.

Primary Hyperparathyroidism and Calcinosis:

• Nephrocalcinosis and renal stones
• Cholelithiasis
• Chondrocalcinosis
• Calcification at ectopic sites such as blood vessels, cardiac valves, skin, etc.—metastatic calcification

Note: Soft tissue calcification and tumoural calcinosis occur in secondary hyperparathyroidism.

Parathyroid Glands

Hyperparathyroidism Investigations:

Investigations can be classified as follows:

1. To prove hyperparathyroidism:

• Serum calcium, phosphate, albumin
• Serum PTH assay
• Alkaline phosphatase
• X-ray of bones.

2. To localise parathyroid glands

• Ultrasound of neck
• Thallium and technetium subtraction scan
• Selective venous sampling with PTH assay. This is most reliable but more difficult.
• Sestamibi scanning.

1. To Prove Hyperparathyroidism

1. Serum calcium levels are always raised above normal limits (9–11 mg%). There are many causes of hypercalcaemia which are depicted in Key Box 38.5. Hence, estimation of serum calcium alone will not give the diagnosis.
2. Albumin is the main calcium binding protein in the plasma. Hence, it should also be measured.
3. Serum PTH level which is estimated by immunoassay is the diagnostic investigation. It is called tumour marker for hyperparathyroidism. Estimation of PTH is difficult, costly and needs sophisticated set up.
4. Serum phosphorus levels are decreased.
5. Alkaline phosphatase is increased when bones are involved.

Causes of Hypercalcaemia:

Interesting Radiological Changes

• Osteopenia
• Bone density loss in cortical bone—radius
• Bone cysts and
• Aggregation of osteoclasts brown tumours (osteoclastoma)
• Rugger Jersey spine
• Generalised loss of bone density
• Pepper pot skull
• Demineralised bone— mottled appearance
• Subperiosteal
• Seen in radial aspect of resorption middle phalanges of 2nd (pathognomonic) and 3rd fingers, bone cysts and tufting of the distal phalanges

2. To Localise Parathyroid Glands:

1. High frequency ultrasound of the neck can be very accurate in the hands of an experienced sonologist. It can also detect renal disease, pancreatic disease, etc. It cannot scan behind sternum and cannot pick up lesions less than 0.5 cm. Specially useful in detecting intrathyroidal parathyroid adenoma (sensitivity is about 75%).
2. Thallium-technetium isotope scan: First the thyroid is outlined with 99mTc and then isotope 201TICl (thallium chloride) is administered. This is taken up by both the thyroid and parathyroid. By computer subtraction of the two and enlargement of images, the parathyroid appears as a hot spot.
3. Technetium 99m (99mTc)–labelled sestamibi (MIBI) scanning: MIBI (methyl-isobutyl-isonitrile radionuclide—sestamibi is concentrated in tissues rich in mitochondria)

• Heart
• Salivary glands
• Thyroid glands
• Parathyroid glands

This test has proved to be superior to thallium and technetium subtraction scanning.

• Sestamibi is a protein labelled with technetium 99m that localises diseased gland—most widely used and is an accurate modality.
• It is very sensitive to identify adenomas (90%) than hyperplasia.

However, it is very expensive. Hence, it can be used in ‘Re-exploration of neck’ for parathyroidectomy.

4. SPECT: Single Photon Emission Computed Tomography when used with sestamibi is useful in evaluation of ectopic parathyroid adenomas—deep in the neck or mediastinum.

Hyperparathyroidism Indications For Surgery:

1. Symptomatic hyperparathyroidism
2. Serum calcium greater than 20 mg%
3. Renal stones
4. Hypercalciuria (>400 mg/day)
5. Decreased creatinine clearance by 30%
6. Reduced cortical bone density

Hyperparathyroidism Treatment:

Parathyroid Glands

1. Intraoperative recognition of parathyroid:

1. Radioguided parathyroidectomy—it is possible if there is a preoperative MIBI scan.
2. Frozen section has failure rates about 2–3%.
3. Intraoperative tissue aspirate PHT—in primary HPT.
4. Methylene blue is not recommended because of the risk of toxic encephalopathy.

2. Surgery: The surgery of the parathyroid glands needs patience, skill and expertise. The neck is explored with a collar neck incision (3–4 cm) caudal to cricoid cartilage.

• Parathyroid gland, when it is enlarged can be dark-brown or chocolate brown colour.
• Occasionally, the surgeon is lucky to encounter a single adenoma usually located on the posterior surface of the thyroid gland, when it arises from superior parathyroid.
• Very often, identification of the parathyroid may be difficult because they may be intrathyroidal or within the mediastinum.

Identification of Parathyroid at Surgery:

• Bloodless field is necessary.
• Ligate middle thyroid vein. Then, retract thyroid gland medially and anteriorly.
• Identify inferior thyroid artery and recurrent laryngeal nerve.
• Parathyroids are covered by fat.
• Incise fat lobule.
• Parathyroid ‘pops out’.

When you cannot Identify at Surgery?

• Divide thyrothymic ligament.
• Search in tracheoesophageal groove.
• Call for intraoperative ultrasound to rule out intrathyroidal gland.
• Incise and look inside carotid sheath.
• Remove thymus—send it for frozen section.
• Sometimes parathyroid can be more than 4.
• Do sternotomy—last step.

Frozen section of parathyroid glands is essential to confirm whether it is an adenoma or hyperplasia because treatment depends upon the pathology of the gland.

1. Single adenoma: Excision of the gland. However, one other normal parathyroid gland is also removed for histopathological study.

2. Diffuse hyperplasia: 3½ or 3¾ parathyroids are removed and small pieces are autotransplanted into the forearm muscle tissue. In case there is hyperactivity of this parathyroid tissue, surgical exploration becomes easy. At the same time, if this functions normally, patient will not develop hypoparathyroidism (13–14 pieces of 1 mm each in brachioradialis)

Parathyroid autotransplantation:

• Indicated after removal of all four parathyroids and in HPT with renal failure.
• 1 mm × 1 mm × 2 mm pieces are made from parathyroid tissue and placed in sterile iced saline.
• It is transplanted in patient’s nondominant forearm within fibres of brachioradialis.
• 4 to 5 pieces (about 100 mg) are transplanted.
• Sutured with silk.
• It will take 14–21 days for parathyroids to function.

Cryopreservation Of Parathyroid Glands:

• Patients who became a parathyroid after re-explorations specially in MEN syndrome, are candidates for cryopreservation.
• Here 200 mg of cut parathyroids tissue is frozen in solutions containing 10% dimethyl sulfoxide, 10% autologous serum and 80% Weymouth solution.

Exploration of the neck and parathyroidectomy:

• Preoperative localisation of gland is preferable.
• Rapid intraoperative PTH measurement after minimally invasive parathyroidectomy should be done.
• Fall in PTH is highly indicating of the success.
• More often it is a single adenoma—it is removed and rest normal glands are left undisturbed.
• If one cannot identify parathyroids glands, look for ectopic glands—posterior and deep to thyroid gland, in the tracheoesophageal grooves, posterior to inferior thyroid vessels between carotid artery and oesophagus.

3. Carcinoma: All four glands should be removed along with ipsilateral thyroid lobe with modified radical neck dissection in the presence of lymph node metastasis radical parathyroidectomy

Preoperatively Suspect Parathyroid Carcinoma when:

• Severe symptoms
• Serum calcium levels greater than 14 mg/dl
• Significantly elevated PTH levels
• Swelling of parathyroid gland

Follow-up:

• Estimation of calcium should be done in the postoperative period to assess the functioning of the parathyroid tissue. Very often, after surgery for adenoma, there is a sudden drop in the levels of calcium because of absorption of the calcium by the bones.
• This is described as ‘hungry bone syndrome’. This is seen in patients who have generalised bone disease.
• In one of our patients, calcium levels dropped down to 4 mg% with severe tetany. It took 7–10 days for it to return to the normal levels. She required 24 hr constant infusion of calcium.
• Absorption of calcium can be enhanced by oral administration of 1,25 dihydroxycholecalciferol, which is the most active metabolite of vitamin D. Vitamin D stimulates the absorption of calcium and phosphate.

Parathyroid Glands

Recent Advances In Parathyroid Surgery

Cervicoscopy:

1. Minimally invasive endoscopic parathyroidectomy (MIP):

• This is possible today because of localisation by ultrasound/sestamibi combined with SPECT
• Popularised by Gagner
• Indicated for a single adenoma
• Can be done under general anaesthesia or regional—cervical block by using xylocaine (1%) with adrenaline
• 3–4 trocars are required
• CO2 insufflation is required

2. Video-assisted parathyroidectomy—minimally invasive:

• It is popularised by Parlo Miccoli from Italy
• Ideal for a single adenoma without thyromegaly
• No previous neck surgeries
• It can be done without CO₂ insufflation— gasless
• Bleeding, recurrent laryngeal nerve injuries are not uncommon
• Can be done for bilateral cases
• No trocars, a small 2–3 cm incision

3. Totally endoscopic parathyroidectomy by lateral approach by Henry, et al. It is the choice for adenoma deeper to thyroid gland. Not for bilateral cases. 10 mm endoscope is required. Require CO₂ insufflation.

Primary Hyperparathyroidism (PHPT)—Interesting ‘Most’

• Mostly it is sporadic.
• Mostly it is due to single adenoma.
• Most abundant cation in the body is calcium.
• Most common and earliest manifestation of MEN type I is PHPT.
• Most common presentation of PHPT is asymptomatic hypercalcaemia.
• Most widely used and accurate investigation for localising parathyroid gland is sestamibi scan.
• Most commonly done surgery for PHPT is excision of adenoma.

Clinical Notes:

• A 20-year-old boy attended dental outpatient department for a loose tooth. He was diagnosed to have a loose tooth and a cyst in the lower jaw as confirmed by X-ray.
• Patient also had genu valgus deformity with backache. An ortho opinion was sought for. Investigations revealed high calcium levels. An ultrasound neck revealed a parathyroid adenoma of 6 cm.
• At exploration a single adenoma was found arising from right inferior parathyroid and was excised. Incidentally, X-ray abdomen also revealed bilateral nephrocalcinosis.
• This case illustration has been given to highlight the various presentations of hyperparathyroidism. High degree of suspicion is necessary for a clinician to consider the possibility of hyperparathyroidism.

Acute Hypercalcaemic Crisis

• Also called parathyroid crisis.
• It presents with severe abdominal pain and effortless vomiting. Dehydration, oliguria, renal failure follow soon. Drowsiness and confusion are other features.
• Untreated cases develop coma and cardiac arrest.
• Profound muscular weakness is characteristic.

Parathyroid Crisis Causes:

1. Hyperparathyroidism:

Sudden increase in PTH levels occur due to spontaneous bleeding in a parathyroid tumour or rupture of a cystic parathyroid tumour. Severe dehydration also precipitates a crisis.

2. Disseminated carcinoma with bony metastasis (usually from carcinoma of the breast).

3. Parathyroid carcinoma:

Parathyroid Crisis Investigations:

• Hypercalcaemia (16 to 20 mg/dl)
• Azotemia abnormal high level of urea, cratinine, etc.

Parathyroid Glands

Parathyroid Crisis Treatment:

1. Restore fluid volume urgently: 300 to 500 ml/hr of 0.9% sodium chloride (normal saline) 5 to 10 L/day IV should be given. It not only helps in volume restoration but also helps in renal excretion of calcium. Inj. furosemide (80 to 100 ml) can be given after volume restoration.

2. Bisphosphonates—disodium pamidronate slow 15–60 mg single IV infusion or over 2–4 days. Maximum dose is about 90 mg. This drug stops mobilisation of calcium from the bone.

3. Mithramycin: It is produced by Actinomyces, Streptomyces plicatus. Given in high doses of 20–25 µg/kg/ IV over 4 to 6 hours/day for 3 to 4 days. Can have beneficial effects. However, effect seems to be temporary. Used in all cases of malignant hypercalcaemia.

• Avoid thiazide diuretics. Cases which do not respond to corticosteroids can be treated with mithramycin.
• Mithramycin rapidly controls hypercalcaemia of malignant disease in most of the patients. This control sometimes is temporary, and intermittent administration of the antibiotic was required.

4. Steroids (in cases of vitamin D intoxication and sarcoidosis).
5. Gallium nitrate therapy is highly effective and superior to maximally approved doses of calcitonin for acute control of cancer-related hypercalcaemia. It inhibits bone resorption increasing calcium containing bone in majority of patients.

Calciphylaxis

Etiopathogenesis:

• It is also called calcific uremic arteriolopathy. It is seen in end stage kidney disease patients or patients with secondary hyperparathyroidism who are undergoing parathyroidectomy.
• A few other conditions which can predispose to calciphylaxis are inflammatory bowel diseases, autoimmune diseases, etc.
• Obesity, diabetes, corticosteroids, chronic liver disease are a few risk factors. It occurs due to extensive disseminated calcification of vessels and skin necrosis.

Etiopathogenesis Clinical Features:

• Patients develop expanding painful cutaneous lesions which are purpuritic.
• Extremities and areas wherein fat contents are more such as breast, buttocks and abdominal wall, gets affected often.
• Due to high levels of calcification, ischemic necrosis occurs, and it results in gangrene. Once gangrene sets in sepsis and death occur.

Etiopathogenesis Diagnosis:

It is based on the clinical features and high levels of calcium, phosphate and with or without high levels of PTH.

Etiopathogenesis Treatment:

• Renal transplantation is the definite treatment for secondary hyperparathyroidism. A few drugs used to treat this are calcimimetic drugs.
• They reduce the stimulation of parathyroid glands and thus lower the PTH levels. If it is associated with persistent high levels of PTH—more than 500 pg/ml total parathyroidectomy with autograft in the nondominant forearm brachioradialis muscle or subtotal parathyroidectomy wherein three and half parathyroid are removed.