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5 Prophylactic Thyroidectomy

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Table 5.2 Timing of surgery based on RET mutation based on 1999 consensus statement from the Seventh International Workshop on Multiple Endocrine Neoplasia

Risk

RET mutation

level

codons

A 609, 630, 768,

790, 791, 804, 891

B 609, 611, 618,

620, 630

C 634 <3–5years >3–5years >3–5years Before 5years of age D 883, 918, 922 <1year

Timing of RET testing

<3–5years >3–5years >3–5years Before 5–10years of age

<3–5years >3–5years >3–5years Consider surgery before age

Timing of rst serum calcitonin testing

≥6months if surgery delayed

Timing of rst US Recommended surgery age

5years; may be delayed beyond age 5years if criteria met

<1year <1year

As the presence of RET gene defect leads to near 100% certainty of MTC, the only question is the timing prophylactic surgery balancing the risk of surgery on patients with the risk of developing malignancies. Both prospective and retrospective data comparing the use of positive DNA testing for RET versus serum biochemical evaluation with calcitonin levels have shown that DNA testing leads to predictable and more accurate risk assessment for patients [9]. Studies have shown that patients undergoing thyroidectomy for increased calcitonin levels were older than those undergoing surgery for positive DNA testing [18, 21]. Similarly, the risk of medullary thyroid cancer is much higher in those who already have elevated levels of calcitonin in their blood [18, 21]. The timing of surgery therefore should predate the rise in serum calcitonin and presence of thyroid nodules based on ultrasonographic evaluations.

Following diagnosis of MTC based on ne needle aspiration in an index patient or from a patient following conrmation of genetic heritage, patients will need either screening or surgical intervention. In patients with MEN II syndromes, associated endocrinopathies such as pheochromocytoma and hyperparathyroidism need to be excluded or evaluated to minimize the risk of concurrent disease. Those patients undergo screening with either plasma-free metanephrines or 24-h urine collection for metanephrines to rule out pheochromocytoma which can increase the risk of thyroidectomy if not previously discovered. Presence of hyperparathyroidism also needs to be conrmed because of the need to alter surgical plan to possibly include parathyroidectomy concurrently. Patients with

delayed surgical intervention should have serum calcitonin and CEA levels checked along with periodic thyroid ultrasonography to evaluate for presence of thyroid nodules. In patients with RET proto- oncogene defect, the screening for pheochromocytoma should commence by 11years of age in highest risk individuals (MEN2B).

Once the RET gene defect has been identied, clear-cut ATA guidelines exist regarding the timing of surgery since risk of MTC development increases incrementally (Fig. 5.2). For patients with FMTC and MEN2A, RET codon defects such as 609, 630, 768, 790, 791, 804, 891 should undergo screening evaluation and possible prophylactic thyroidectomy before the age of 10. Children with codon defects including 609, 611, 618, 620, 630 need to consider surgery by 5years of age. Those with codon 634 defect is the most common type of MEN2A and also at particularly increased risk of malignancy. Therefore, patients with codon 634 defect need to undergo surgery by 5years of old. Finally, patients with MEN2B are at the highest risk for MTC.Surgery should not be postponed much beyond 1year of age in these high-risk individuals, even with the elevated risk of surgical morbidity [9, 22–24].

5.3 Cowden Syndrome/PTEN

Hamartoma Tumor Syndrome

Cowden syndrome, named after the patient of the same last name, was rst described in 1962 [25]. This syndrome was described in a patient with

before 1 year of age

X. Da Dong and R. Lati

Exclude Pheo / Evaluate

Adult

RET Positive

Children

Fig. 5.2 Schematic workup following identication of RET proto-oncogene defect

for

HPTH

MEN2A (low risk)

MEN2A (mod risk)

MEN2B (high risk)

ndings of multinodular goiter, papillomas of the oral mucosa, cystic breast diseases, and CNS abnormalities. Patients of this syndrome seem to have a familial pattern of inheritance. Subsequent investigations into this cluster of syndromes led to the identication of other ndings commonly seen with Cowden syndrome [26–29]. Patients often have concurrent trichilemmomas, acral keratoses, and bromas. The phenotypic abnormalities did not end with its early description. Other unusual ndings in some patients with Cowden syndrome included Lhermitte–Duclos disease with its phenotypic dysplastic cerebellar gangliocytoma and gastrointestinal hamartomas. During the 1990s, genetic linkage studies were able to identify a tumor suppressor gene, phosphatase and tensin homolog gene (PTEN), as possible cause for up to 80% of patients developing the constellation of ndings [26, 30]. With this nding, another group of patients were also found to have PTEN mutations but other phenotypic appearances. Patient with Bannayan– Riley–Ruvalcaba syndrome was found to have PTEN gene defect in up to 60% of patients. These patients have early-onset macrocephaly, gastrointestinal hamartomas, vascular malformations, Hashimoto’s thyroiditis, and penile freckling [27–29, 31]. Patients with either somatic or hereditary PTEN mutations are associated with breast, thyroid, renal, endometrial, colorectal, and melanoma-type malignancies.

Subsequently, with increasing recognition, patients with PTEN hamartoma tumor syndromes are diagnosed based on clinical criteria developed by the International Cowden Consortium [4, 5].

Measure Serum

Calcitonin

Total thyroidectomy before

10 years of age or when

calcitonin rises

Total thyroidectomy before

5 years of age

Total thyroidectomy w/wo

level VI node dissection

Patients with Cowden syndrome with underlying germline PTEN mutations are at increased risk of breast, thyroid, endometrial, and renal cancers. The majority of patients with Cowden syndrome are diagnosed in a de novo fashion. Following discovery of their rst malignancy, the development of secondary malignancy is reportedly as high as 40%, in comparison to about 18% in the general population [32].

Initial presentation of a new patient with PTEN hamartoma syndrome can be quite difcult to recognize due to diverse clinical presentations. However, since secondary cancer risk is elevated compared with normal population, it is important to identify this group of patients following initial workup because of their risk for developing another malignancy. Several features of patients with PTEN hamartoma syndrome that are rare in the general population include the following: (1) Lhermitte–Duclos disease (dysplastic cerebellar gangliocytoma), (2) extreme macrocephaly, (3) oral mucosal papillomatosis, (4) penile freckling, (5) hamartomas and ganglioneuromas of the gastrointestinal tract, (6) glycogenic acanthosis, (7) differentiated thyroid cancer in pediatric patients, and (8) early-onset endometrial cancer [25, 31–33].

Because of the increased recognition of this underreported disease, there is now the Cleveland Clinic PTEN risk calculation tool which can help determine a percentage risk for PTEN mutation analysis. Patients with high-risk scores will need genetic counseling and testing. Identication of patients with PTEN gene defect should alert the clinician to increased scrutiny and testing

Calcitonin < 500 pg/ml Total thyroidectomy

Calcitonin > 500 pg/ml

Screen for Pheo by

16 years

11 years

Evaluate for systemic

disease and treat

Follow calcitonin, if >

150 pg/ml, evaluate for

metastatic disease

5 Prophylactic Thyroidectomy

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of patients [32, 34]. Additionally, prior cancer in these patients increases the risk of secondary cancers in patients with PTEN hamartoma syndrome. Therefore, these patients may benet from prophylactic surgeries or therapeutic interventions [32].

The lifetime risk of patients with germline PTEN mutation for development of malignancies is high. Collectively, based on several studies, the risk of female breast cancer ranges from 67 to 85% [33]. Risk of DTCs is lower but ranges from 25 to 38%. Similar to breast cancer, the risk is higher in women for thyroid cancer than men [33]. Patients also have signicant risk of developing endometrial and renal cell carcinomas. Since the risk of developing thyroid cancer is not 100%, patients with PTEN mutations following genetic diagnosis benets from screening thyroid ultrasounds to look for cancer development. Surveillance of patients with PTEN mutations frequently leads to discovery of combination of multiple nodules, goiter, and/or Hashimoto’s thyroiditis. Patients can also develop thyroid cancer in PTEN mutation positive cohorts at an early age. Therefore, ultrasound evaluation of thyroids should start as soon as the condition of Cowden syndrome or PTEN hamartoma tumor syndrome is diagnosed in a patient.

Although PTEN mutation was initially thought to be the culprit for the multitude of different variable phenotypic expression, it is now clear that Cowden syndrome is genetically also heterogenous making nal recommendations regarding prophylactic surgery especially difcult. Up to 25% of patient meeting Cowden syndrome diagnostic criteria have been found to have negative PTEN mutations. Some patients with Cowdenlike syndrome have some features of Cowden syndrome but do not always meet diagnostic criteria or have the germline mutations. These patients can harbor other germline mutations such as succinate dehydrogenase variants (SDHB/C/D), PIK3CA, AKT1, and hypermethylation of KILLIN gene [30]. Hypermethylation of KILLIN, which is a tumor suppressor that affects PTEN, can result in the under expression of PTEN [30].

Treatment of patients with PTEN hamartoma tumor syndrome associated thyroid cancer is

frequently a total thyroidectomy. These patients tend to have concomitant thyroid nodules, goiter, and/or thyroiditis in addition to thyroid cancer. In addition, with increased risk of another thyroid cancer in the future, total thyroidectomy seems to be the rational choice for these patients. In terms of prophylactic thyroidectomy, this is an area that is hotly debated, especially after diagnosis of a previous cancer or discovery of benign thyroid nodules or goiters. Prophylactic thyroidectomy needs to be carefully weighed against risks for surgery in patients to minimize morbidity and follow-up mandates. There is a role of prophylactic thyroidectomy in a subset of patients with Cowden syndrome. Since some patients are unable to adequately follow-up for serial ultrasonic examinations of their neck, prophylactic thyroidectomy has been proposed as an option for patients with cognitive decits who make thyroid ultrasound follow-up difcult to accomplish [32].

5.4 Hereditary Syndrome atRisk forThyroid Pathology

Familial forms of follicular cell-derived neoplasms constitute approximately 5–15% of nonmedullary thyroid cancers [35]. In addition to the genetically and phenotypically heterogeneous Cowden/Cowden-like syndrome, several other familial syndromes can lead to a high rate of thyroid diseases and thyroid neoplasia. Notably, non-medullary thyroid cancers have been found with greater frequency in patients with familial adenomatous polyposis (FAP), Carney’s syndrome, DICER1-related syndrome and Werner’s syndrome among others. In patients with these syndromes, their thyroid carcinomas tend to be part of heterogeneous diseases, and often has early-onset, multicentricity and bilateral tendencies [35].

Several of the known hereditary cancer syndrome that causes thyroid cancer are autosomal dominant. Both MTC and Cowden syndrome are autosomal dominant hereditary cancer syndrome which leads to an increased risk of thyroid cancer [36–38]. Cowden syndrome is a disease

X. Da Dong and R. Lati

is both genetically and phenotypically heterogeneous which makes it difcult to determine the exact risk for thyroid cancer. Unfortunately, multiple other genetic conditions that predispose at-risk individuals to thyroid cancer are also heterogeneous in presentation, therefore careful workup of patients with thyroid pathology is a necessity (Table5.3).

Familial adenomatous polyposis (FAP) is known to lead to increased risk of differentiated thyroid cancer (DTC). The defect caused by the adenomatous polyposis coli (APC) gene carries a risk of up to 12% for development of DTC.In FAP, this autosomal dominant syndrome is caused by germline mutation in the APC gene on chromosome 5q21. Pathognomonic ndings are the presence of hundreds of adenomatous colonic polyps that develop early on necessitating total colectomy by the age of 40. Papillary thyroid cancer has a female preponderance and is one of the many extracolonic manifestations of FAP, occurring in 2% of patients. Young women are at particularly higher risk for development of thyroid cancer and their risk is estimated to be 160 times that of normal individuals [35]. These patients frequently have bilateral, multifocal disease and histologically display a rare cribriform pattern. The cells are usually well differentiated and have a spindle pattern, often associated with marked brosis. The cribriform-morular variant of PTC, which in contrast to conventional PTC, rarely metastasizes and carries a benign prognosis. Because of the rare occurrence of this type of tumor, its identication raises the possibility of undiagnosed FAP. Patients diagnosed with conventional FAP should also be alerted to the possibility of concurrent thyroid pathology. Intensive screening for thyroid nodules is recommended after the age of 15 years. Prophylactic surgical intervention should also be considered following identication of thyroid nodules. In this patient cohort, it is advisable to perform total thyroidectomy as management of newly discovered thyroid nodules due to the possibility of bilaterally and the high incidence of subsequent thyroid pathology.

Carney’s complex is an autosomal dominant disease characterized by skin and mucosal pig-

mentation [39]. Carney’s complex is a condition where there is a gene defect in PRKAR1A gene, leading to the development of blue nevi. Patient with this condition has a relatively lower incidence of DTC, compared to other hereditary cancers, although higher than the general population. These patients often have a variety of endocrine neoplasias as well, including pituitary adenomas, pigmented nodular adrenal disease, and Sertoli and Leydig cell tumors [39]. Patients with Carney’s complex usually present with multinodular goiter with adenomatous nodules. Approximately 5–15% of patients with Carney’s complex will eventually develop either papillary thyroid cancer (PTC) or follicular thyroid cancer (FTC). Nonetheless, although thyroid cancer risk is increased in these types of patients, the majority are actually aficted with thyroid goiters leading to the occasional need for thyroid surgeries.

Patients with DICER1 defect are recently undergoing closer scrutiny in terms of their risks for malignancies. These patients most commonly develop pleuropulmonary blastomas which are characterized by tumors that grow in lung tissue or the pleura [6]. Other malignancies seen with DICER1 syndrome include cystic nephromas, Sertoli-Leydig cell tumors of the ovaries, and thyroid cancer. The patients with DICER1 syndrome are known to be at risk of multinodular goiter with occasional development of DTCs. However, recent investigations into DICER1 mutations have uncovered a group of early-onset poorly differentiated thyroid cancers in adolescents and young adults that are pathologically aggressive. This may lead to changes in terms of management options in patients with DICER1 syndrome [6].

Patients with Werner’s syndrome develop a curious phenotype of premature aging. Patients with this syndrome are also at increased risk of a variety of neoplasia including benign thyroid nodules and DTCs. Patients with Werner’s syndrome have close to 18% risk of developing thyroid cancers with the majority being PTCs [3, 19]. A smaller percentage does develop FTC or the aggressive anaplastic thyroid cancer. Although incidence of DTCs is elevated with Werner’s syndrome, the risk is still low that only

5 Prophylactic Thyroidectomy

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Incidence of

thyroid

neoplasia

0.4–12%

Type of thyroid

neoplasia

PTC

(cribriform-

morular

Extracolonic polyps, congenital

hypertrophy of retinal pigment

epithelium, soft-tissue tumors,

<5%

variant)

FV-PTC

(follicular

variant PTC)

PTC

desmoids, osteomas

Thyroid multinodular goiter, melanotic

–

FTC

schwannomas, adrenal or pituitary

FTC

FV-PTC

PDTC

adenomas, hepatocellular carcinoma,

pancreatic cancer

Wilms tumor, rhabdomyosarcoma,

ciliary body medulloepithelioma,

pineoblastoma, pituitary blastoma,

35%

PTC

FV-PTC

nasal chondromesenchymal

hamartoma

Fibrocystic breast disease,

gastrointestinal hamartomas, lipomas,

bromas, renal cell carcinomas,

18%

PTC

uterine bromas

Melanoma, soft tissue sarcomas, liver

FTC

cancers, myelodysplastic syndrome

Other major diagnostic

features Minor features

Colonic adenomatous

Gene defect

(chromosomal

location) Pathognomonic feature

APC

Hereditary syndrome

Table 5.3 Predisposition syndromes for differentiated thyroid cancer

APC-associated polyposis

polyps

(5q21-q22)

(familial adenomatous

polyposis, attenuated FAP,

Gardner syndrome, Turcot

syndrome)

Pigmented nodular

adrenals, cardiac

myxomas

Ovarian sex cord-

stromal tumors, cystic

nephroma, thyroid

multinodular goiter

Multiple pigmented skin

lesions (e.g., nevi, blue

nevi, lentigines)

Pleuropulmonary

blastoma

(17q24.2)

“CNC2” (2q16)

Carney complex PRKAR1A

(14q32.13)

DICER1 syndrome DICER1

Breast, endometrial,

thyroid cancer,

macrocephaly

Mucocutaneous lesions,

cerebellar tumors

(Lhermitte-Duclos

disease)

Breast, endometrial,

PTEN

(10q23.2)

PTEN hamartoma tumor

syndrome (Cowden,

Bannayan-Riley-Ruvalcaba,

PTEN-related proteus,

proteus-like syndromes)

Heart disease,

thyroid cancer,

macrocephaly

Werner syndrome WRN (8q12) Premature aging,

cataracts, short stature,

decreased fertility,

type 2 diabetes

scleroderma-like skin

changes

PTC papillary thyroid cancer, FTC follicular thyroid cancer, PDTC poorly differentiated thyroid cancer, FV-PTC follicular variant of papillary thyroid cancer

X. Da Dong and R. Lati

enhanced surveillance is recommended without the need for prophylactic thyroidectomy.

Management decisions in patients with thyroid nodules or goiter are inuenced by their predisposing hereditary conditions. Even with small tumors (<1 cm), risk of multifocal disease and subsequent neoplasia would favor more aggressive surgical intervention. Therefore, total thyroidectomy often needs to be considered for treatment for small tumors that are incidentally discovered [3, 19].

Patients with Beckwith–Wiedemann syndrome, the familial paraganglioma syndromes, Li-Fraumeni syndromes, McCune-Albright syndrome, and Peutz-Jeghers syndrome are all examples of hereditary syndromes with increased incidence of thyroid cancer [19, 35, 40]. However, the tumors that develop in these patients may not be a direct result of gene defect leading to thyroid neoplasia but rather a global phenomenon due to impaired DNA repair leading to higher incidences of neoplasms. As such, these patients are not routinely considered for prophylactic thyroid surgery or even enhanced mode of surveillance for their thyroid pathologies [40].

5.5 Risk ofProphylactic

Thyroidectomy

Surgeon attitude towards prophylactic thyroidectomy has changed signicantly with regard to management of hereditary MTC. With genetic sequencing and the risk of malignancy carried by each mutation, timing of surgery can predate the onset of neoplasia. However, surgery on earlyonset MTC can also lead to signicant morbidities including permanent hypoparathyroidism and recurrent laryngeal nerve injury. Using the National Inpatient Sample hospital discharge data, patients younger than 17 years old undergoing thyroidectomy/parathyroidectomy showed signicantly higher risks compared to their adult counterparts [41, 42]. Complication rates for patients separated into age groups (0–6 years,

7–12years, and 13–17years) showed an inverse relationship of complications with age groups. Children that are in the 0–6 age group had complication rates as high as 22% compared to 11% for age group of 13–17 [41, 42]. Based on retrospective single-center data, surgical risks are signicant in very young patients who are at risk for hereditary MTC [22, 42]. Risk of transient hypocalcemia is as high as 27% and permanent hypocalcemia can be as high as 20% in patients younger than 5years old [22, 42]. Therefore, risk of surgery needs to be explained and carefully balanced with the risk of development of MTC.

5.6 Conclusions

Surgeon attitude and patient understanding towards management of organ-specic disease entities have changed dramatically over the years. With decreases in surgical morbidity and a clearer understanding that certain genetic conditions predispose patients to malignancies or long signicant morbidities, primary organ resection with replacement hormone therapy became an appealing longterm solution over short-term interval surveillance. Due to the availability of genetic screenings for potentially fatal MTC, prophylactic thyroidectomy is one of the few procedures where patients can expect near certainty on the effectiveness of their surgery in reducing risk of cancer. Increasingly, other heritable conditions that lead to increased risk of thyroid malignancy are also being elucidated on their malignancy potential. The role of prophylactic thyroidectomy in these conditions may expand as the accuracy in predicting subsequent malignancy improves, and the risk of surgery becomes less than that of malignancy. Furthermore, the surgical approach in small incidentally discovered tumors would entail total thyroidectomy to prevent subsequent malignancies [3].

Acknowledgment None.

Conicts of Interest None.

5 Prophylactic Thyroidectomy

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009- 0370- 2.

Prophylactic Parathyroidectomy

Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/

MariaCastaldi, SachaRoberts, andRifatLati

6.1 Introduction

Four parathyroid glands are present in most individuals, but supernumerary, or a fth parathyroid has been reported in 6–13% of cases and may arise from division of one or more of the four parathyroid glands during development [1]. The parathyroid glands are located in the anterior neck, posterior to or within the thyroid gland, although may be found from the angle of jaw to the arch of aorta, and weigh 35–40mg each. They have an important role in the biochemical milieu of the body and dysfunction of hyperparathyroids (hyper or hypoparathyroidism) is associated with serious metabolic consequences that may lead to major morbidity and mortality. Both superior and inferior parathyroid glands, with their blood

M. Castaldi (*) New York Medical College, School of Medicine, Valhalla, NY, USA

Department of Surgery, Westchester Medical Center, Valhalla, NY, USA e-mail: maria.castaldi@wmchealth.org

S. Roberts New York Medical College, School of Medicine, Valhalla, NY, USA e-mail: sroberts19@student.nymc.edu

R. Lati Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, NY, USA e-mail: rifat.lati@wmchealth.org;

Rifat_Lati@nymc.edu

supply from the inferior thyroid artery, are quite vulnerable to injury during thyroidectomy.

The principal function of the parathyroid glands is regulation of calcium metabolism and homeostasis by direct effects on the kidney, bone, and gastrointestinal tract through PTH actions. While detailed description of the biology and metabolic activities of parathyroid hormone and its relationship with calcium and phosphorus hemostasis is beyond the scope of this chapter, it is important to mention that no study or treatment of parathyroid gland dysfunction can be effective without thorough understanding of anatomy, biology, recent advances in early diagnosis, localization of the pathology, intraoperative localization, and postoperative management of these complex patients. Most recent surgical textbooks provide comprehensive reviews of the subject.

Parathyroidism is the third most common endocrine disorder, after diabetes and thyroid disease. It can be primary, secondary, and tertiary. Primary hyperparathyroidism (PHPT) is caused mainly by three major conditions: parathyroid adenoma (80–90%), parathyroid hyperplasia hormone (PTH) (10–15%), and multiple endocrine neoplasia (MEN1 and MEN2). Finally, on very rare occasions (<1%), parathyroid carcinoma is a cause of primary HPT.Two disorders that must be distinguished from PHPT are familial hypocalciuric hypercalcemia (FHH) and hypercalcemia of malignancy. Both can be diagnosed with simple but careful analysis of biochemical tests.

M. Castaldi et al.

The rst condition is associated with an abnormal biochemical prole.

Secondary hyperparathyroidism is caused by multiple contributing factors including possible genetic mutation, altered vitamin D metabolism and resistance, impaired calcium response to PTH, retention of phosphorus, and altered metabolism of PTH [2]. The parathyroid glands are intrinsically normal in secondary hyperparathyroidism; however, progressive derangements due to abnormal calcium homeostasis ensue.

Tertiary hyperparathyroidism, on the other hand, is rare and occurs in only two conditions: in patients with secondary hyperparathyroidism when parathyroid glands become autonomous and hypercalcemia ensues; the second setting is in transplant patients that do not become eucalcemic because parathyroid glands become autonomous. This occurs in 8.5–53% of transplant recipients, 1% of who will require parathyroidectomy.

Historically, at least two patients have entered the annals of parathyroid surgery as most spectacular failures of parathyroidectomy. Charles Martell, the rst parathyroid patient operated on at the Massachusetts General Hospital for severe primary hyperparathyroidism, underwent neck exploration seven times before his parathyroid was found in the mediastinum [3]. Albert Jahne, operated on by Felix Mandl, died of osteitis brosa cystica, from four-gland hyperplasia that was not cured with parathyroidectomy [4]. Both Albert Jahne and Charles Martell had persistent or recurrent disease and died of the devastations of uncontrolled hyperparathyroidism. Both cases provided enormous contributions to elucidating the function of the parathyroid glands.

6.2 Conditions toConsider

forProphylactic Parathyroidectomy

Parathyroidectomy is a relatively rare operation. For example, high-volume surgeons are considered those surgeons with >50 cases per year, and in most countries these operations are performed by endocrine surgeons. Surgeons performing 1–15 cases per year are considered

lower volume surgeons. Experienced higher volume surgeons have lower rates of persistent or recurrent PHPT [5–7].

Despite signicant diagnostic and surgical advances in parathyroidectomy, the optimal timing for surgical treatment in patients with asymptomatic primary HPT is not well established, and controversy exists between high-volume and low-volume surgeons. Obviously, those with high-volume believe that patients should be operated early, prior to disease manifestation associated with primary HPT, while those with lower volume do not. Although physicians may be cautious recommending surgery for asymptomatic patients, NIH has developed criteria for surgery for asymptomatic patients [8]. Surgery thus rests on the premise of future health benets as well as cure rates that are highest when performed by high-volume surgeons.

6.3 Osteitis Fibrosa Cystica (OFC)

Osteitis brosa cystica is a skeletal disorder characterized by loss of bone mass that occurs secondary to PHPT.Elevated levels of PTH cause increased osteoclast activity and consequent bone resorption. This leads to softening of the bones and fractures. Lytic lesions may also develop due to the many multinucleated osteoclast cells. Overt skeletal involvement is extremely rare in most developed countries with prophylactic removal of the parathyroid glands.

OFC can be reversible with removal of the parathyroid gland(s) that contain the adenoma with the goal of preventing advanced skeletal changes. One study of 51 patients with PHPT and skeletal disease or OFC proved a near disappearance of bone pain and regaining of muscular strength in 36 (70.6%) patients by just 1 week following parathyroidectomy [9]. Additionally, all patients with fractures (n= 33) experienced complete healing of the fractures by a median time of 3months postoperatively after parathyroidectomy. Symptomatic hypocalcemia was evident in 46 (90.2%) patients soon after surgery; however, studies have demonstrated low rates of permanent hypocalcemia [9, 10].

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