* - IN FOLLOW UP MAINTAIN ADEQUATE HYDRATION, EXERCISE & NORMAL CALCIUM DIET. AVOID THIAZIDE DIURETICS, LITHIUM & EXCESSIVE CALCIUM INPUT.
* - MEASURE S. CALCIUM, CREATININE, PTH, 24 HRS URINE CALCIUM, CREATININE CLEARANCE, FRACTIONAL EXCRETION OF CALCIUM, ABDOMINAL X-RAY & DEXA BONE DENSITOMETRY ( LUMBER SPINE, FEMER, FOREARM ) ANUALLY.
HYPERPARATHYROIDISM IS SUBDEVIDED INTO THREE TYPES :
1. PRIMARY CAUSED BY
- SINGLE ADENOMA ( 85%) & MULTIPLE GLANDS ARE INVOLVED IN ( 15%) & RARELY PARATHYROID CANCER
- FAMILIAL : AS PART OF MEN 1 OR MEN 2A, HYPERTHYROID-JAW TUMOR SYNDROME, FAMILIAL ISOLATED HYPERPARATHYROIDISM, FAMILIAL HYPOCALCIURIC HYPERCALCEMIA & NEONATAL SEVERE HYPERPARATHYROIDISM
2. SECONDARY
3. TERTIARY
Medical care
The diet of individuals with primary hyperparathyroidism should include around 1200-1500 mg of calcium per day. Also, 400 IU of vitamin D per day is reasonable. Estrogen therapy in postmenopausal women has been shown to cause a small reduction in serum calcium and increases in BMD, with stable PTH. However, risks are associated with estrogen replacement. Raloxifene may be an alternative. Alendronate has also been shown to increase the spine BMD in patients with primary hyperparathyroidism. Calcimimetic drugs may be an alternative in the future.
Other medical therapy is limited to the treatment of hypercalcemia itself. In the acute setting, this can be accomplished by the use of intravascular volume expansion with sodium chloride and loop diuretics such as furosemide once the intravascular volume is restored. In rare cases, hypercalcemia has been treated with bisphosphonate therapy as a temporary measure prior to surgical treatment.
Surgical care
Indications for surgery
Symptomatic hyperparathyroidism should be treated by surgical excision of the abnormal glands.
Some clinicians advocate surgical therapy in all patients with primary hyperparathyroidism, modified only for those patients who are not able to tolerate surgery. They argue that the operation is generally well tolerated and such treatment prevents complications (eg, osteoporosis) and may reverse symptoms that patients often do not realize they have (eg, fatigue, depression). Others advocate a nonsurgical approach whenever possible, such as in patients with a calcium level less than 11.5 mg/dL, patients with no apparent symptoms, and patients who have normal 24-hour urine calcium excretion and no osteoporosis.
A National Institutes of Health (NIH) Workshop on Asymptomatic Primary Hyperparathyroidism in 2002 revisited the key management issues addressed at the 1990 NIH Consensus Development Conference. They recommended new guidelines for surgery and the conservative approach of monitoring patients who do not meet the criteria for surgery. The indications for surgery as per the 2002 guidelines are as follows:
1.0 mg/dL above the upper limit of the reference range for serum calcium
24-hour urinary calcium excretion greater than 400 mg
A 30% reduction in creatinine clearance
Bone mineral density T-score below -2.5 at any site
Age less than 50 years
For monitoring of patients with asymptomatic hyperparathyroidism who do not undergo surgery, the following are recommended: serum calcium and creatinine levels every 6 months and annual bone mineral density (all 3 sites).
Choice of surgical treatment
The standard operative approach is complete neck exploration with identification of all parathyroid glands and removal of all abnormal glands. In the case of 4-gland hyperplasia, a 3.5-gland (subtotal) parathyroidectomy is performed. Approximately 50-70 mg of the most normal-appearing tissue is left behind. A nonabsorbable suture is left as a tag to identify the gland should reoperation be necessary.
Approximately 85% of cases of primary hyperparathyroidism are caused by a single adenoma. Therefore, most patients who undergo full neck exploration to evaluate all parathyroids endure some unnecessary dissection. Rather than explore all parathyroid glands, a newer technique, directed parathyroidectomy, has evolved. This technique relies on preoperative imaging studies to localize the abnormal gland. The surgeon then removes only that gland, without visualizing the other glands.
With either sestamibi scanning or ultrasonography, an abnormal parathyroid may be detected preoperatively in 70-80% of cases. However, neither technique is reliable for detecting multiple abnormal glands. Therefore, an additional method is required to confirm that no other abnormal glands are present after excision of the imaged lesion.
For this purpose, many centers have begun to use the intraoperative PTH assay. Because the plasma half-life of PTH is only approximately 4 minutes, the level falls quickly after resection of the source. If the level fails to fall after resection of the identified abnormal gland, the procedure is extended to allow for further exploration. However, the intraoperative PTH assay is expensive and is usually available only in centers that perform a high volume of parathyroidectomies.
A few authors have advocated radio-guided parathyroidectomy, detecting the labeled sestamibi in the abnormal gland using a handheld probe. The excised radioactivity in the abnormal parathyroid is then compared with the remaining background to confirm excision of all affected glands. However, most centers have abandoned this technique because (1) if the gland labels well with sestamibi, use of the handheld probe intraoperatively is unnecessary in most cases and (2) the use of background counts to confirm complete excision of all abnormal tissue has not been well validated.
Use of directed parathyroidectomy results in a more limited operation for most patients, resulting in a more rapid recovery. However, it may yield a higher persistence rate than complete neck exploration, and it probably should be performed only in centers with the capability to perform the intraoperative PTH assay.
For familial disease, such as MEN 1, total parathyroidectomy is performed with autotransplantation to the forearm and cryopreservation of some parathyroid tissue.
Preoperative care
Parathyroidectomy is usually well tolerated. The main risks are those associated with anesthesia. Although local anesthesia has been used successfully for this procedure, especially in the directed approaches where a single adenoma is localized preoperatively, general anesthesia is used most commonly.
In patients in whom hypercalcemia (and, therefore, dehydration) has been severe, special attention must be directed to perioperatively restoring the fluid balance.
Neck mobility must be assessed to ensure proper positioning in the operating room.
If the patient's voice is normal, preoperative documentation of vocal cord function is not necessary.
Intraoperative details
Complete parathyroid exploration
The most critical aspect to ensure success in this operation is identification of all 4 parathyroid glands and removal of all abnormal glands.
The patient is placed in the lawn-chair position with the neck extended over a transversely placed shoulder roll. This position allows full exposure of anterior neck structures and improves venous drainage.
A low transverse incision placed within the skin creases provides the best cosmetic result. The length of the incision must be adequate to allow thorough exploration of all potential locations of the parathyroid glands; however, given the elasticity of the neck skin flaps, a 3- to 5-cm incision allows safe identification of important structures.
After hemostasis of the skin incision is obtained, subplatysmal flaps are developed superiorly to the notch of the thyroid cartilage and inferiorly to the flat portion of the manubrium. The sternohyoid and sternothyroid (strap) muscles are separated in the midline to expose the thyroid gland. If preoperative localization studies suggest a parathyroid adenoma, that side is approached first.
Frequently, a middle thyroid vein may require ligation to ensure adequate mobilization of the thyroid lobe. The thyroid lobe is elevated off the common carotid artery and retracted medially. The inferior thyroid artery is identified after blunt and sharp dissection of the areolar tissue anteriorly and medially to the common carotid artery and posteromedially to the thyroid lobe. The recurrent laryngeal nerve is identified next, inferior and lateral to the lower lobe of the thyroid gland.
The intersection of the inferior thyroid artery and the recurrent laryngeal nerve is an important landmark because most parathyroid glands, superior and inferior, are located within 2 cm of this area. The superior parathyroid glands are located dorsal to the upper two thirds of the thyroid lobe and posterior to the recurrent laryngeal nerve. The inferior glands, which are less consistent in location, can usually be found inferior to the inferior thyroid artery and ventral to the recurrent laryngeal nerve. They are usually within 1 cm of the inferior lobe of the thyroid gland.
Abnormally enlarged glands are excised after confirmation of the normal size of other glands. During excision, avoiding capsular rupture of the abnormal gland is important because this may be associated with implantation of parathyroid cells in the operative site and subsequent parathyromatosis. Parathyroids may be identified by highly experienced surgeons based on appearance and location. In most cases, identification of the parathyroid glands should be confirmed histologically by frozen section examination. In all cases of subtotal or total parathyroidectomy with autotransplantation, parathyroid tissue must be cryopreserved for future autotransplantation if the initial transplants are not functional.
Directed parathyroidectomy
In many respects, the operative technique is similar to that described above for a complete parathyroid exploration. Differences are noted below.
Adequate imaging of the abnormal gland prior to surgery is essential. In addition, arrangements for intraoperative measurement of PTH should be confirmed. A line for sampling of peripheral venous blood should be established. Often the distal saphenous vein provides the most convenient access.
Some surgeons modify the location of the incision based on the preoperative location of the adenoma. This author prefers a small incision (ie, ~2 cm) in the standard location for a collar incision. This incision can be readily extended should a complete exploration prove necessary.
A baseline PTH level is drawn immediately prior to skin incision. Following identification and dissection of the adenoma, a preexcision level is drawn. Manipulation of the gland occasionally causes significant increases in the PTH level. Following excision of the gland, PTH levels are drawn at 5 minutes and 10 minutes postexcision. Criteria for adequate excision are either: a 50% drop in PTH from the baseline level to the 10-minute post-excision level or a 50% drop in PTH from the preexcision level at 10 minutes and a postexcision level below the baseline level.
The incision may be closed while the last PTH levels are being processed, but the patient should remain under anesthesia and the sterile field maintained until the PTH assay results are known.
Ectopic parathyroid glands
Occasionally, all parathyroid glands cannot be identified. In such instances, the usual locations are reexamined first because most parathyroid glands are located in typical areas. If parathyroid glands are not identified in those locations, then a systematic search is performed, taking into consideration the path of descent of superior and inferior parathyroid glands.
Inferior glands may be located in the thyrothymic ligament. They may be difficult to identify, especially after division of the inferior thyroid vein, a maneuver that allows the gland to retract into the superior mediastinum. Another location for ectopic inferior parathyroid glands is the thymus. The thymus can be visualized through a transverse cervical incision by retracting the innominate vein dorsally with a sponge-stick while elevating the manubrium anteriorly. Division of the interclavicular ligament improves visualization in the superior mediastinum.
Superior parathyroid glands are usually dorsal to the upper two thirds of the thyroid gland. Occasionally, these glands are adjacent to the superior thyroid vessels. Other locations include the carotid sheath or posterior to the esophagus or pharynx (retroesophageal). Finally, both superior and inferior parathyroid glands may be located aberrantly within the capsule of the thyroid gland. Some surgeons perform a thyroid lobectomy on the side harboring the abnormal gland after an exhaustive search is made in the aforementioned locations. Median sternotomy is rarely required during the initial neck exploration for hyperparathyroidism.
Postoperative care
If a directed parathyroidectomy is performed successfully, most of these patients may be safely discharged the day of surgery. Some practitioners routinely supplement with oral calcium postoperatively.
For a full parathyroid exploration, calcium levels must be monitored postoperatively every 12 hours until stabilization. The nadir of serum calcium usually occurs 24-72 hours postoperatively. Many patients become hypocalcemic, but few become symptomatic. Reserve treatment for hypocalcemia unless it is severe or the patient becomes symptomatic.
Hypocalcemia after parathyroid surgery may be due to hungry bone syndrome where calcium and phosphorus are rapidly deposited in the bone. This is characterized by hypoparathyroidism and transient, but occasionally severe, hypocalcemia until the normal glands regain sensitivity.
If hypoparathyroidism persists, oral supplementation with calcium and vitamin D is required. Calcium citrate or calcium carbonate may be started at 2 tablets 4 times per day. Some patients require more or less. Calcitriol is started at 1 mcg/d for 1 day, 0.5 mcg/d for 2 days, and then 0.25 mcg/d thereafter. Patients in whom an autotransplantation is performed require temporary calcium supplementation.
If a recurrent nerve injury is suggested because the patient has developed new hoarseness, immediate laryngoscopy is indicated. If vocal cord paralysis is observed, immediate reoperation may be warranted to repair a transected nerve because a few of these may regain function. Reexploration after 24-48 hours is not generally indicated because the risks of operating in an inflamed field outweigh the relatively low likelihood of a benefit.
A potential life-threatening emergency in the postoperative period is the development of an expanding hematoma in the pretracheal space. This complication must be recognized and treated immediately by opening the wound and evacuating the hematoma. If untreated, laryngeal edema may progress rapidly, causing airway obstruction.
Most small hematomas do not require treatment. A subplatysmal fluid collection may occasionally form, and these are usually treated adequately with a single aspiration. In a few cases, aspiration may need to be repeated. Rarely, a drain may need to be placed for recurrent fluid collections.
Follow-up
Patients are seen 1-2 weeks postoperatively, and serum calcium and PTH levels are obtained. PTH levels may be elevated postoperatively in some patients, but if the serum calcium remains within the reference range it does not indicate persistent disease in most patients.
After the immediate postoperative period, follow-up is limited to periodic determinations of serum calcium levels to detect the persistence or recurrence of disease or hypoparathyroidism.