Issues in parathyroid surgery

ISSUES IN PARATHYROID

SURGERY

Dr Sachin KatyalPost Graduate StudentDepartment of General Surgery MKCG Medical College, Berhampur.

AIM OF THE TOPIC

Aim of the topic is to highlight the clinical features, diagnosis, and treatment of parathyroid disease which have changed radically over the past 25 years as a result of technologic advances in the fields of laboratory medicine, radiology, medicine, and surgery. In particular, there have been many technical advances in the surgical management of primary hyperparathyroidism (HPT) and with these advances have come the issues and controversies…….

A FEW FACTS TO APPRECIATE

There are 4 parathyroid glands, lie on the posterior surface of the thyroid.

The superior glands are located on the poster medial aspect of the thyroid near the tracheoesophageal groove.

The inferior parathyroids are more widely distributed in the region below the inferior thyroid artery .

Common sites for ectopic parathyroids are thyrothymic ligament, superior thyroid poles, tracheoesophageal groove, retroesophageal space, carotid sheath

A FEW MORE FACTS….

The average weight of a normal PTH gland is 35 to 40 mg; in adults, its color turns to yellow as the fat content increases.

The inferior PTH originate from the 3rd branchial pouch, whereas the superior parathyroids descend from the 4th branchial pouch.

The superior and inferior parathyroid glands receive their blood supply from the inferior thyroid artery in 80% of cases.

SOME MORE FACTS TO REMEMBER..

Each parathyroid gland generally receives a single end-artery blood supply that is vulnerable to injury during surgical manipulation.

The glands are made up of chief and oxyphil cells, as well as fibrovascular stroma and adipose tissue.

TYPES OF HYPERPARATHYROIDISM

PRIMARY

SECONDARY

TERTIARY

3 PATHOLOGIC LESIONS LEADING TO PRIMARY PTH

1, PARATHYROID ADENOMA

2. PARATHYROID HYPERPALSIA

3. PARATHYROID CARCINOMA

3 PATHOLOGIC LESIONS LEADING TO PRIMARY PTH CONTINUED

1.PARATHYROID ADENOMA-benign encapsulated neoplasm- responsible for 80-90% cases.

2.PTH HYPERPLASIA –proliferation of parenchymal cells –affects all parathyroid glands-responsible for 10-15% cases.-multigland hyperplasia have sporadic disease.

also associated with multiple endocrine neoplasia(MEN)

type 1 (primary HPT combined with lesions of the pancreas and pituitary)

type 2A (primary HPT, medullary thyroid cancer, and pheochromocytoma) syndromes.

PTH HYPERPLASIA is not a part of Type 2B –but includes MEDULLARY CA OF THYROID, PHEOCHROMOCYTOMA AND MUCOSAL NEUROMA

3 PATHOLOGIC LESIONS LEADING TO PRIMARY PTH CONTINUED……

3.PARATHYROID CARCINOMA - a slow-growing, invasive neoplasm of parenchymal cells responsible < 1% of cases of primary HPT.

Although fibrosis and mitotic activity are common, they are not specific for malignancy.

For diagnosis of carcinoma invasion of blood vessels, perineural spaces, soft tissues, thyroid gland, or other adjacent structures, or tumors with documented metastases are must.

It is often difficult for the pathologist to make this diagnosis, especially if there is only a frozen section analysis of a resected parathyroid gland.

Secondary Hyperparathyroidism- the pathogenesis of secondary HPT has

multiple contributing factors, like genetic mutations, altered vitamin D metabolism and resistance, impaired calcemic response to PTH, retention of phosphorus, and altered metabolism of PTH.

In all cases of secondary HPT, the failing kidney is unable to hydroxylate vitamin D2 to active vitamin D3 (calcitriol)

ROLE OF PARATHYROIDECTOMY IN SECONDARY HYPERPARATHYROIDISM

ROLE OF PTH SURGERY IN SECONDARY HPT

Although secondary HPT is typically managed initially with non operative strategies, there are pathophysiologic sequelae of chronic renal failure that serve as indications for parathyroidectomy.

post parathyroidectomy patients have shown improvement in physical activity and increase in muscle force measurements and also improvements in anemia.

ROLE OF PARATHYROIDECTOMY IN TERTIARY HYPERPARATHYROIDISM

TERTIARY.- Tertiary HPT occurs in a subset of

patients with secondary HPT in whom the parathyroid glands become autonomous and hypercalcemia develops.

Can occur even post transplantation, when secondary HPT persists.

ROLE OF PTH SURGERY IN TERTIARY HPT CONTINUED

Surgical treatment of tertiary HPT is reserved for patients without resolution of symptoms, for those with hormonal and chemical abnormalities such as elevated or increasing iPTH(intact PTH) levels and an increase in serum calcium levels to higher than 12.0 mg/dL that persists more than 1 year after transplantation

for those with acute hypercalcemia (calcium level >12.5 mg/dL) in the immediate post-renal transplant period.

ROLE OF PARATHYROID SURGERY IN MEN-1 ASSOCIATED HYPERPLASIA

Parathyroid surgery in patients with MEN1 is thought of as a debulking or palliative procedure because recurrence is inevitable, because it is indicated to treat and prevent the complications of HPT.

The initial surgical procedure of choice in a patient with MEN1 and HPT is subtotal parathyroidectomy or total parathyroidectomy with heterotopic auto transplantation of resected parathyroid tissue; transcervical thymectomy is also performed at the initial operation

ROLE OF PARATHYROID SURGERY IN MEN-2A

When compared with HPT in MEN1, HPT in MEN2A tends to be milder and more often asymptomatic because of a single adenoma, although multiglandular hyperplasia does occur. Therefore, curative resection can be less aggressive.

Enlarged parathyroids encountered during thyroidectomy for medullary thyroid cancer in a normocalcemic patient are resected.

Most, but not all endocrine surgeons leave normal appearing parathyroids in situ, although total parathyroidectomy with auto transplantation to the forearm has been advocated by some.

WHAT ARE THE ISSUES IN PARATHYROID SURGERY?

Controversy regarding patient selection.

Controversy regarding if surgery is providing a substantial benefit.

Controversy regarding the need for pre-op localization.

Controversy regarding the superiority of intra-operative localization over pre-operative localization.

PATIENT SELECTION- WHO REALLY NEEDS IT?

Even though a National institutes of health consensus conference was held in 1990, another workshop in 2002 and the latest one in 2008,there is still no consensus among endocrinologist and endocrine surgeons about whether to administer non-operative medical therapy and monitor or to refer them for early parathyroidectomy.

However, because of long term deleterious effects of bone mineralization, the pendulum has shifted to surgical intervention.

CRITERIA FOR SURGICAL REFERRAL

Criteria for surgery has been established according to the best evidence to date……

Serum calcium concentration >1 mg/dl above upper limits of normal.

Bone density at lumbar spine, hip, or distal end of radius that is > 2SD below peak bone mass

(T- score<-2.5) All individuals with primary

hyperparathyroidism and <50yr Patients for whom medical surveillance is

undesirable or impossible.

IS THERE A SUBSTANTIAL BENEFIT OF PARATHYROIDECTOMY?

Good response to parathyroidectomy has been shown in following:

1.Neuromuscular symptoms of primary PTHProximal muscle weaknessRespiratory muscle capacity.2.Psychiatric symptoms Mental dullnessConfusionDepression.3.Significant and durable increase in bone mineral density in the

lumbar spine and hip apparent within 6 months of surgery.4.Urinary ca excretion and nephrolithiasis reduced by surgery However No effect of successful surgery noted on HTN or renal

impairment.

PRE-OP LOCALIZATION-REALLY NEEDED?

Dopmann, a radiologist…once said

“only localization test necessary was to locate a good endocrine surgeon” but this maxim has been proved outdated as image –guided targeted approach has reduced morbidity in a big way.

There has been a paradigm shift in use of preoperative imaging in primary hyperparathyroidism

Major advances in imaging studies has led to development of more localized surgery, with the opportunity for shorter operation times, the use of local or regional anesthesia, and limited or no hospital stay.

PRE-OPERATIVE IMAGING IN PATIENTS WITH PRIMARY HYPERTHYROIDISM

NON-INVASIVESestamibi

Sestamibi SPECTUltrasound

4D CTMRI

PET CT

INVASIVEangiography

Venous localizationUltrasound, biopsy

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Physiologic areas of increased tracer uptake include the thyroid, salivary glands, heart and liver

SESTAMIBI SCAN DEMONSTRATING LEFT INFERIOR PARATHYROID ADENOMA.

SESTAMIBI SCAN

1- works by mitochondrial uptake of 99mTc sestamibi,and parathyroid cells typically have a large number of mitochondria.

2- Sestamibi, a monovalent lipophilic cation, is preferentially concentrated in adenomatous and hyperplastic parathyroid tissue because of increased blood supply, higher metabolic activity, and absence of P-glycoprotein on the cell membrane

.

SESTAMIBI SCAN CONTINUED….

3-Sestamibi imaging can be performed preop. for Minimally Invasive Parathyroidectomy planning , or in the morning of surgery in the operating room in conjunction with the use of a gamma probe to guide the surgeon during surgery

LIMITATIONS OF SESTAMIBI

false-positive results on sestamibi scans. overcome in part by using the double-tracer

subtraction technique of sestamibi, in which both thyroid and parathyroid nodular abnormalities can be diagnosed simultaneously, or in combination with neck ultrasonography to distinguish thyroid lesions and parathyroid adenomas preoperatively.

Sestamibi scans are now being performed with simultaneous CT imaging to yield correlative functional and anatomic localization

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4D-CT showing increased uptake on delayed phaseimaging of a parathyroid adenoma (arrow).

4D CT

4 dimensional CT , a novel imaging modality similar to CT angiography, is derived from 3 dimensional CT scanning with added changes in perfusion of contrast over time.

It generates detailed multi-planar images of the neck and allows the visualization of differences in perfusion characteristics of hyper functioning parathyroid gland.

4D CT images provide anatomic and functional information

IMAGES OF 4 D CT SCAN

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ULTRASOUND IMAGE OF A HYPOECHOIC PARATHYROID ADENOMA

Ultrasound is effective, noninvasive, and inexpensive, butits limitations include operator dependency and restriction to application in the neck because it cannot image mediastinal parathyroid lesions

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ANGIOGRAM SHOWING THE ADENOMA AS A CLASSIC BLUSH IN THE RIGHT POSTERIOR POSITION(ARROW)

ANGIOGRAPHY Meant for patients who require re-

exploration— noninvasive localization studies will have negative, discordant, or non-convincing results

This technique requires catheterization of multiple veins in the neck and mediastinum, from which blood samples are obtained.

Since results of PTH measurement performed in the angiography suite are available quickly,interventional radiologists can obtain additional samples from a region in which a subtle, but potentially significant, PTH gradient is detected.

ANGIOGRAPHY CONTINUED……

Because parathyroid adenomas have increased vascularity, they have a characteristic blush on arteriography.

This use of interventional radiology rarely causes serious complications such as visual field defects or other cerebrovascular events, but such studies are time-consuming and expensive .

USG GUIDED FINE NEEDLE ASPIRATION OF SUSPICIOUS LESION

ultrasound localization can be used to guide fine-needle aspiration of a lesion suspicious for a parathyroid adenoma.

This technique can be used with rapid PTH measurement of the parathyroid aspirate in the ultrasound suite to give ultrasonographers immediate feedback so that they can continue searching for an abnormal parathyroid gland if the aspirate of the suspicious lesion is negative.

INTRA-OPERATIVE LOCALIZATION

Intraoperative PTH ASSAY

RADIOGUIDEDPARATHYROIDECT

OMY

INTRAOPERATIVE PTH ASSAY

The rapid intraoperative PTH assay can be used to confirm adequate removal of hyper secreting parathyroid

A peripheral blood specimen is obtained immediately before surgery.

Repeat blood samples are then drawn intraoperatively immediately after resection of the enlarged gland(s) to capture a potential hormone spike caused by manipulation of the gland during extirpation, and then 5 and 10 minutes after excision.

INTRAOPERATIVE PTH ASSAY

A 50% reduction in the PTH level from baseline is used as an indication that the exploration has been successful..

The rapid PTH assay is especially helpful when the surgeon has difficulty distinguishing between thyroid tissue, lymph nodes, or a parathyroid adenoma.

CONTROVERSY REGARDING INTRAOP PTH MEASUREMENTS

false negative predictions from the test lead to unnecessary exploration.

Cost factor although there continues to be some

controversy, the largest endocrine surgery centers use the assay as an important adjunct to MIP.

In patients with multigland disease in particular intraoperative PTH testing has been shown to be essential

RADIOGUIDED PARATHYROIDECTOMY

Hand held Gamma counter with a probe

In radio guided parathyroidectomy,10 to 20 mCi of 99mTc-sestamibi is injected IV 2 to 4 hours before surgery, and the adenoma is localized intraoperatively with a hand-held quantitative gamma counter with a 9- to 14-mmprobe.

Gamma counts are obtained at the start of the operation in all four quadrants of the neck, through the skin, and after the incision, under the strap muscles.

.

RADIOGUIDED PARATHYROIDECTOMY CONT.

Exploration in which counts are highest focuses surgery and reduces operative time.

The activity of the removed parathyroid is checked with the gamma probe to confirm cure.

The excised adenoma emits radioactivity at least 20% and often 50% in excess of the post excision background.

Finally, the post excision radioactivity in all four quadrants of the neck should equalize.

CONTROVERSY REGARDING RADIOGUIDED PARATHYROIDECTOMY

gamma probe provides functional feedback to the surgeon helping in intraoperative decision making.

particularly helpful in the setting of false-positive sestamibi scans, ectopic parathyroid adenomas, and remedial parathyroidectomy in which attempts at localization have been suboptimal.

Still, intraoperative use of the gamma probe has not been embraced by most experienced endocrine surgeons because it yields little additional information over that obtained by adequate preoperative localization and the intraoperative PTH assay.

PTH SURGERIES BROADLY CLASSIFIED INTO TRADITIONAL AND MINIMALLY INVASIVE

TraditionalBilateral neck explorationGeneral anesthesiaAll parathyroid glands are identifiedIntraop frozen sectionPatients admitted for 1-2 days

Minimally invasive

Unilateral neck

explorationRegional or

local anesthesiaExcision of

culprit gland

Preoperative

localizationAmbulatory

patient

MINIMALLY INVASIVE PARATHYROIDECTOMY

A focused exploration is performed according to the results of the preoperative imaging study, and the intraoperative PTH assay is used to confirm the adequacy of resection in the operating room.

MIP was associated with a 50% reduction in operating time and 7fold reduction in length of hospital stay which represents a reduction in total hospital charges by almost 50%.

TECHNIQUE OF MINIMALLY INVASIVE PARATHYROIDECTOMY

Unilateral neck exploration under local or regional anesthesia

A, A small transverse cervical skin incision is made, the platysma is divided, and the anterior jugular veins are preserved.

B, The raphe between the strap muscles is divided in the midline.

C, The parathyroid adenoma is excised, with care taken to preserve the recurrent laryngeal nerve and minimize manipulation of the tumor during ligation of the end artery.

.

VIDEO-ASSISTED PARATHYROIDECTOMY It does not require steady gas flow, but

rather a brief insufflation of carbon dioxide to establish the operative space, which is then maintained by external retraction.

Preoperative localization is essential and general anesthesia is typically used, although local anesthesia might be feasible.

A 15-mm skin incision is created 1 cm above the sternal notch to accommodate tactile assessment, suction irrigation, and dissection and retraction equipment.

.

VIDEO ASSISTED PARATHYROIDECTOMY CONTINUED……

Another 10-mm trocar site is made vertically in the midline below the strap muscles and above the thyroid gland on the ipsilateral side of the suspected adenoma to accommodate the insufflator at the start of the case;

a 30-degree, 5-mm endoscope is then inserted with two retractors for moving the thyroid medially and the strap muscles laterally.

ENDOSCOPIC PARATHYROIDECTOMY Patients with mediastinal parathyroid

adenomas can undergo thoracoscopic removal.

Access for the endoscope is obtained at the manubrium and two additional ports are inserted laterally in the neck, anterior to the sternocleidomastoid muscle and ipsilateral to the parathyroid tumor

The operative space is created between the platysma and strap muscles by using insufflation at low pressure (5 to 8 mm Hg), and the strap muscles and thyroid are mobilized to expose the parathyroid

.

PROBLEMS WITH VIDEO ASSISTED PARATHYROIDECTOMY

there is a significant learning curve associated with endoscopic parathyroidectomy.

Even with low insufflation pressure, there can still be problems with small amounts of blood obscuring the field of view, metabolic disturbances from carbon dioxide absorption, subcutaneous emphysema.

the operative space can be lost during suction there is no opportunity for tactile assessment.

REMEDIAL PARATHYROIDECTOMY

Remedial parathyroidectomy is often required for symptomatic persistent and recurrent HPT.

Persistent HPT is defined by an inability to achieve normalization of the serum calcium level after initial exploration and represents an immediate technical failure.

Recurrent disease is defined by initial normalization of the serum calcium level but then delayed hypercalcemia after 6 months of eucalcemia.

REMEDIAL PARATHYROIDECTOMY CONT. Preoperative localization and use

of the rapid intraoperative PTH assay are important adjuncts for enhancing success rates during remedial parathyroid surgery.

Perhaps the best indication for 4D-CT is in the setting of remedial neck surgery.

In cases of reexploration,it can be useful to have cryopreservation available because the only remaining parathyroid tissue might be the site of persistent or recurrent disease.

POSTOPERATIVE COMPLICATIONS The rate of persistent HPT can be as

high as 30% in less experienced hands. Injury to the RLN or nerves, leading to

hoarseness or frank airway compromise if both nerves are injured .

Superior laryngeal nerve injury results in subtle voice changes, which can have profound deleterious effects in professional singers or speakers.

Intraoperative monitoring of the RLN using specialized equipment allowing for recording and documenting of electromyography signals of vocal cord function have been introduced.

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PARATHYROID ADENOMA WITH THE THYROID GLAND ABOVE AND THE RECURRENT LARYNGEAL NERVE SPLAYED AROUND IT (TIP OF THE FORCEP)

COMPLICATIONS CONTINUED……

Hematomas and wound infections are uncommon. The risk for these complications is theoretically less when exploration is confined to one side of the neck.

Hypoparathyroidism from injury to or removal or devascularization of the remaining parathyroids can occur and result in hypocalcaemia.

CONTROVERSY REGARDING ASYSMPTOMATIC HPT

The principal debate is whether patients should be treated with early surgery or whether surveillance or medical therapy can be used safely until symptoms develop.

Patients with elevated PTH levels and consistently normal serum calcium levels, in whom secondary causes of hyperparathyroidism have been excluded, may represent the earliest presentation of primary HPT.

It is believed that during this early phase, termed normocalcemic hyperparathyroidism, elevated serum PTH levels cause a reduction in cortical bone density

.

CONTROVERSY REGARDING ASYMPTOMATIC PTH

many of such patients had a history of kidney stones (14%),fragility fractures (11%), and osteoporosis (57%) over the course of up to 8 years.

During follow-up, 40% developed further signs of primary HPT, such as hypercalcemia, renal stones, fractures, or bone loss.

normocalcemic HPT can have substantial skeletal involvement and may represent an early form of symptomatic, rather than asymptomatic, primary HPT.

CARRY HOME MESSAGE

Hyperparathyroidism is increasingly being recognized as a result of the detection of hypercalcemia by widespread use of multiphasic screening.

symptoms in patients are subtle or absent. Parathyroidectomy is a highly successful treatment for

some patients with asymptomatic primary hyperparathyroidism may have a prolonged benign course.

Significant and durable increase in bone mineral density in the lumbar spine and hip apparent within 6 months of surgery.

Pre-operative as well intra-operative localization have a role to play in successful surgery proving the dictum wrong that only localization necessary is a good endocrine surgeon .

REFERENCES

Sabiston 19 the edition Bailey and love 26th edition

THANK YOU……..

Special thanks to Prof Dr SK Das Sir for giving his precious time and moderating the presentation and my Sir Dr S.S. Mohanty for being a guiding force in everything that I am able to do…….