1. The multiple symptoms of primary HPT can be summarized by the aphorism ‘bones, stones, groans, and psychic moans’. However, 80% of patients are asymptomatic and present incidentally with the finding of hypercalcaemia on routine blood testing for other medical conditions. Very rarely, patients may present with significant bone disease (osteitis fibrosa cystica), most clearly seen on X-rays of the middle phalanges showing subperiosteal bone resorption. This presentation tends to occur more frequently in severe longstanding disease, parathyroid cancer or secondary and tertiary hyperparathyroidism.

2. The biochemical diagnosis of hyperparathyroidism requires the demonstration of persistently raised levels of serum calcium with an associated high serum parathormone (PTH) level, or a level that is inappropriately normal in the presence of high serum calcium levels. Normocalcaemia does not exclude hyperparathyroidism and some patients with renal stones have been shown to have high PTH levels in the presence of a normal serum calcium. Always consider and exclude other causes of hypercalcaemia. In particular, familial hypercalcaemic hypocalciuria (FHH) can be confused with it since it presents a similar biochemical profile. Order urinary calcium estimations to exclude this condition. Hypocalciuria (less than 2 mmol/day) should prompt the diagnosis of familial hypercalcaemic hypocalciuria.

3. You have a responsibility to ensure that, whatever the referral pathway, potential reversible causes of secondary hypercalcaemia (including lithium therapy and vitamin D deficiency) have been excluded, and hereditary conditions identified. The early diagnosis of familial disease is important since the management differs from primary to secondary HPT. The syndromal acronyms are: FHH, ADMH, NSHPT, MEN1, MEN2a, HPT-JT, HPT-IF. (Refer to the landmark article on these acronyms by Marx et al. 2002.)

4. A serum calcium level in excess of 3 mmol/L is an absolute indication for surgery. Consider symptomatic patients for surgery. However, the majority are asymptomatic patients with the discovery of incidental hypercalcaemia during biochemical analysis. A more liberal approach to surgery for asymptomatic patients is developing (see Proceedings of the 3^rd International Workshop JCEM 2009).

5. There is increasing evidence that patients aged 70 years or less have a higher mortality with untreated disease and that this can be reversed by successful parathyroid surgery. Cardiac changes have been shown to be reversed after treatment of asymptomatic disease and symptoms of depression and anxiety may be reversed. Loss of bone mineral content has been shown to be partially reversible, an important factor in postmenopausal women.

6. In secondary hyperparathyroidism, elevated calcium levels can make control of dialysis programmes difficult and can produce significant pathological bone change. It is often accompanied by severe pruritus, muscle weakness and sometimes with soft-tissue calcification. The timing and indications for surgery very much rely on the renal physicians.

7. Once the decision to operate has been made, decide the type of operation needed. In primary HPT, this decision depends upon the patient’s wishes, your competence in the subspecialty, and the success of preoperative localization.

8. The standard operation is a four-gland neck exploration through a cervical collar incision made in a similar way as for exploring the thyroid (see Chapter 20).

9. In 80% of cases, the causative lesion is a solitary parathyroid adenoma, and successful preoperative localization of such a lesion enables you to offer minimally invasive parathyroidectomy using a targeted approach under general or local anaesthesia.

10. In 15–20% of cases, HPT is caused by parathyroid hyperplasia, which may be genetically predetermined. Here, preoperative imaging is far less successful at localizing the causative pathology, and the four-gland exploration is usually more appropriate. Both the targeted approach and four-gland exploration are performed endoscopically in some centres.

11. Explain in preoperative counselling that the same potential risks exist in parathyroid surgery as can occur after thyroid surgery, including recurrent laryngeal nerve injury. There is also the additional risk of failing to find the gland at the first operation, often because it is ectopic.

1. An experienced parathyroid surgeon can cure up to 95% of patients without the benefit of preoperative localization, employing the traditional and more extensive four-gland exploration. However, preoperative localization techniques are now commonly used prior to an initial targeted neck exploration. This is in response to the increasing popularity of daycase parathyroidectomy, minimally invasive parathyroidectomy (MIP), and parathyroidectomy under local anaesthesia.

2. Nuclear scintigraphy is seen as the most accurate localization technique. Technetium Tc 99 m sestamibi, either with a subtraction technique using radio-iodine (I¹²³) or used alone in a ‘double-phase scan’ where the scan is repeated at 2–3 hours, gives the best results. It can localize solitary adenomata in 95% of cases and multigland disease in 80%. The double-phase method relies on the differential washout rate of sestamibi from parathyroid tissue compared to thyroid tissue as a result of the high metabolic rate of the parathyroids, particularly when adenomatous.

3. Ultrasonography is also frequently employed. Results are operator dependent, but in the best hands solitary adenomas can be identified in 93% of cases. Colour Doppler Ultrasound is of limited value when glands are located in the mediastinum.

4. In the detection of ectopic glands, particularly when other tests have failed or following unsuccessful exploration and especially in the identification of suspected mediastinal glands, other forms of imaging may be valuable. Apart from CT or MRI, three-dimensional imaging techniques can be such as single photon emission computed tomography (SPECT). Positron emission tomography (PET) may be carried out either with (¹⁸F)-fluoro-2-deoxy-D-glucose or (¹¹C)-methionine.

5. Venous sampling can be employed if less invasive imaging techniques have failed, when planning revision surgery. This involves central venous catheterization and the subsequent collection of blood samples, measuring intact PTH levels, from the draining veins of the thyroid plexus. Intact PTH assays are measured. Although interpretation of results is hampered somewhat by previous surgery(s) it can be very useful in rough localization of the gland(s) by determining the side, whether it is higher or lower in the neck, or likely to be in the superior mediastinum and thus direct the general area of re-exploration.

6. The patient needs to be well hydrated: if the patient has been admitted in a hypercalcaemic crisis then a period of re-hydration is mandatory before attempting surgery.

1. With the patient in a supine position, and with approximately 30 degrees of reverse Trendelenberg to decrease venous engorgement, extend the neck where possible by appropriate placement of a head ring and sand bag.

2. Make a standard Kocher incision situated midway between the cricoid cartilage and the jugular notch. In most cases it need only be 5 cm long. Continue it through the platysma muscle to the level of the superficial layer of strap muscles. Raise the superior myocutaneous flap to a level at least 2 cm above the cricoid cartilage.

3. Identify the linea alba then separate the strap muscles. Now peel the strap muscles from the ventral surface of one of the thyroid lobes. Begin the search for the parathyroid glands by dislocating the thyroid lobe medially and anteriorly whilst retracting the strap muscles laterally. It is often necessary to divide the middle thyroid vein. Use blunt dissection with pledgets, mosquito forceps and bipolar diathermy division of fine vessels, to maintain absolute haemostasis. In a series of 547 autopsies Gilmour demonstrated that 6% of patients have three and 6% have five glands. In 80% of cases, the position of both the superior and inferior glands on each side is symmetrical – useful to recall when a gland proves difficult to locate.

4. While searching for the superior parathyroid gland the inferior thyroid artery can be readily identified deep to the carotid sheath, usually around the mid-part of the thyroid lobe. Follow it to the thyroid lobe. Now identify the recurrent laryngeal nerve (see Chapter 20). The superior parathyroid glands usually lie behind the upper pole of the thyroid lobe, close to the cricothyroidius muscle. The majority of superior parathyroids are within 1 cm of the cricothyroid joint, above the main branch of the inferior thyroid artery in a plane deep to the recurrent laryngeal nerve. It may be closely adherent to the recurrent laryngeal nerve.

5. The inferior parathyroid glands develop together from the third pouch and descend with the thymus. The majority settle in the neck along this line of descent and separate somewhat from the thymus, which continues into the chest leaving a thyrothymic tract in the neck in which the parathyroid is frequently situated.

6. Mobilize the inferior pole, inspecting particularly in the region of the thyrothymic tract. The gland normally lies on or just below the inferior pole of the thyroid lobe and ventral to the coronal plane of the recurrent nerve. In about 15% of patients it lies distinctly separate from the gland and in the upper pole of the thymus. Its position often allows the excision of an inferior adenoma without recurrent laryngeal nerve identification, provided the dissection proceeds directly on the surface of the gland.

7. The parathyroid glands (often pale brown or tan coloured) are enclosed in an envelope of fat that moves separately from the thyroid. There is usually a small feeding vessel which can be cauterized, ensuring that the gland is not in close proximity to the recurrent laryngeal nerve.

8. During the operation, glands judged macroscopically normal are commonly marked with a Ligaclip. Macroscopically abnormal gland(s) are removed and sent for histology. The procedure can be enhanced by intra-operative frozen section and ioPTH, the latter procedure to confirm cure following a successful dissection, or to point to the need for further exploration.

9. An increasingly difficult problem arises in older people with milder disease forms who are now operated on earlier in their disease process than was previously the case. A solitary adenoma and three ‘normal glands’ can be difficult to distinguish from hyperplasia affecting mainly one gland with mild hyperplasia of the other three. This requires great judgment, and in case of doubt elect to remove three and a half glands. Similarly, if more than one gland is clearly involved, or if this is hyperplasia either from primary or secondary hyperparathyroidism, then elect to remove three and a half glands, leaving approximately 30–50 mg of functional tissue. We advocate this approach as the best way to minimize the risk of recurrence whilst preserving parathyroid function. Some authorities advocate the removal of all four glands, then place the patient postoperatively on calcium and vitamin D supplements to minimize recurrence and surgical failure.

10. Further intra-operative localization strategies are available:

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