Primer hiperparatiroidi, MEN, reküüren ve persistan hiperparatiroidi, sekonder/tersiyer hiperparatiroidi ve paratiroid görüntülemesi
N Engl J Med. 2011 Dec 22;365(25):2389-97.
Clinical practice. Primary hyperparathyroidism.
Marcocci C, Cetani F.
Department of Endocrinology and Metabolism, Section of Endocrinology and Bone
Metabolism, University of Pisa, Pisa, Italy. claudio.marcocci@med.unipi.it
Langenbecks Arch Surg. 2009 Sep;394(5):765-84. Epub 2009 Jul 10.
Imaging for primary hyperparathyroidism--an evidence-based analysis.
Mihai R, Simon D, Hellman P.
Department of Surgery, John Radcliffe Hospital, Oxford, UK.
OBJECTIVE: Imaging in patients with primary hyperparathyroidism has been proven
difficult. During the last decade, sestamibi scintigraphy and ultrasound (US)
have been used with various success. The importance of these procedures has risen
since minimal invasive parathyroid (MIP) surgery also has developed, and it is
claimed that preoperative localization usually is needed before embarking on such
a procedure.
METHODS: We have scanned the most recent literature in this matter in order to
identify evidence, using commonly accepted grading, and also concluded a number
of recommendations.
RESULTS AND CONCLUSIONS: We found evidence at level III leading to
recommendations at grade B, that sestamibi scintigraphy is a recommended first
test, but that US by an experienced investigator may be an alternative. MIP may
be performed when both tests are concordant, and in case of only one test being
positive, unilateral exploration and use of intraoperative PTH measurements are
recommended. Bilateral neck exploration is used when both tests are negative. For
reoperative procedures, repeat investigations are recommended, but also to use
US-guided fine needle aspiration and PTH measurements as well as venous sampling.
However, for reoperative procedures, the level of evidence is weaker-level IV,
but recommendations still at grade B.
World J Surg. 2009 Nov;33(11):2224-33.
Molecular genetics of parathyroid disease.
Westin G, Björklund P, Akerström G.
Department of Surgical Sciences, Uppsala University Hospital, 751 85 Uppsala,
Sweden. gunnar.westin@surgsci.uu.se
BACKGROUND: Primary hyperparathyroidism (HPT) is often caused by a benign
parathyroid tumor, adenoma; less commonly by multiglandular parathyroid
disease/hyperplasia; and rarely by parathyroid carcinoma. Patients with multiple
tumors require wider exploration to avoid recurrence and have increased risk for
hereditary disease. Secondary HPT is a common complication of renal failure.
Improved knowledge of the molecular background of parathyroid tumor development
may help select patients for appropriate surgical treatment and can eventually
provide new means of treatment. The present contribution summarizes more recent
knowledge of parathyroid molecular genetics.
METHODS: A literature search and review was made to evaluate the level of
evidence concerning molecular biology and genetics of primary, secondary, and
familial HPT according to criteria proposed by Sackett, with recommendation
grading by Heinrich et al.
RESULTS: Most parathyroid adenomas and hyperplastic glands are monoclonal
lesions. Cyclin D1 gene (CCND1) translocation and oncogene action occur in 8% of
adenomas; cyclin D1 overexpression is seen in 20% to 40% of parathyroid adenomas
and in 31% of secondary hyperplastic glands. Somatic loss of one MEN1 allele is
seen in 25% to 40% of sporadic parathyroid adenomas, half of which have
inactivating mutation of the remaining allele. Inactivating somatic HRPT2
mutations are common in parathyroid carcinoma, often causing decreased expression
of the protein parafibromin involved in cyclin D1 regulation. Aberrant regulation
of Wnt/beta-catenin signaling may be important for parathyroid tumor development.
CONCLUSIONS: Molecular genetic studies of parathyroid tumors are well designed
basic experimental studies providing strong level III evidence, with data
frequently confirmed by subsequent studies.
J Clin Endocrinol Metab. 2001 Dec;86(12):5658-71.
Guidelines for diagnosis and therapy of MEN type 1 and type 2.
Brandi ML, Gagel RF, Angeli A, Bilezikian JP, Beck-Peccoz P, Bordi C,
Conte-Devolx B, Falchetti A, Gheri RG, Libroia A, Lips CJ, Lombardi G, Mannelli
M, Pacini F, Ponder BA, Raue F, Skogseid B, Tamburrano G, Thakker RV, Thompson
NW, Tomassetti P, Tonelli F, Wells SA Jr, Marx SJ.
Department of Internal Medicine, University of Florence, 50139 Florence, Italy.
m.brandi@dmi.unifi.it
Comment in
J Clin Endocrinol Metab. 2002 Jun;87(6):2994.
This is a consensus statement from an international group, mostly of clinical
endocrinologists. MEN1 and MEN2 are hereditary cancer syndromes. The commonest
tumors secrete PTH or gastrin in MEN1, and calcitonin or catecholamines in MEN2.
Management strategies improved after the discoveries of their genes. MEN1 has no
clear syndromic variants. Tumor monitoring in MEN1 carriers includes biochemical
tests yearly and imaging tests less often. Neck surgery includes subtotal or
total parathyroidectomy, parathyroid cryopreservation, and thymectomy. Proton
pump inhibitors or somatostatin analogs are the main management for oversecretion
of entero-pancreatic hormones, except insulin. The roles for surgery of most
entero-pancreatic tumors present several controversies: exclusion of most
operations on gastrinomas and indications for surgery on other tumors. Each MEN1
family probably has an inactivating MEN1 germline mutation. Testing for a
germline MEN1 mutation gives useful information, but rarely mandates an
intervention. The most distinctive MEN2 variants are MEN2A, MEN2B, and familial
medullary thyroid cancer (MTC). They vary in aggressiveness of MTC and spectrum
of disturbed organs. Mortality in MEN2 is greater from MTC than from
pheochromocytoma. Thyroidectomy, during childhood if possible, is the goal in all
MEN2 carriers to prevent or cure MTC. Each MEN2 index case probably has an
activating germline RET mutation. RET testing has replaced calcitonin testing to
diagnose the MEN2 carrier state. The specific RET codon mutation correlates with
the MEN2 syndromic variant, the age of onset of MTC, and the aggressiveness of
MTC; consequently, that mutation should guide major management decisions, such as
whether and when to perform thyroidectomy.
ANZ J Surg. 2009 May;79(5):378-82.
Outcome of parathyroidectomy for patients with renal disease and
hyperparathyroidism: predictors for recurrent hyperparathyroidism.
Low TH, Clark J, Gao K, Eris J, Shannon K, O'Brien C.
Sydney Head & Neck Cancer Institute, Royal Prince Alfred Hospital, Missenden
Road, Camperdown, NSW 2050, Australia. hubelow@yahoo.com
BACKGROUND: A small group of patients with renal disease-related secondary or
tertiary hyperparathyroidism require surgical parathyroidectomy. Among them,
5-20% require further re-exploration and excision of parathyroid tissue because
of recurrent disease. The aims of the present study were to review the
characteristics and outcomes of patients undergoing parathyroidectomy for renal
disease related hyperparathyroidism and to identify the risk factors for
recurrent hyperparathyroidism.
METHODS: Review of data from a dedicated head and neck database at Royal Prince
Alfred Hospital between 1988 and 2004.
RESULTS: There were 115 patients of whom 68 (59%) patients were treated with
subtotal parathyroidectomy (STP), 43 (37%) were treated with total
parathyroidectomy (TP) and 4 (3%) were treated with TP with autotransplant. Of
those, 11 (9.6%) patients developed recurrent hyperparathyroidism (9 had STP, 1
had TP and 1 had TP with autotransplant). On re-exploration, persistent
hyperplastic parathyroid tissue was located at the site of partially excised
parathyroid gland (64%), autotransplanted parathyroid tissue (9%), anterior
mediastinum (18%) and intrathyroidal parathyroid (9%). Predictors for recurrent
hyperparathyroidism are STP (P= 0.049), preoperative symptom of calciphylaxis or
calcinosis (P= 0.024), elevated preoperative calcium level (P= 0.007) and
elevated post-operative PTH levels (P= 0.014). Post-operative PTH levels less
than 10 pmol/L has a positive predictive value of 97.5% for cure (P= 0.02).
CONCLUSION: More aggressive surgical approach could be indicated in patients with
preoperative hypercalcaemia and calcinosis/calciphylaxis. Post-operative PTH can
be utilized as a marker for cure after parathyroidectomy in hyperparathyroidism
of renal disease.
World J Surg. 2009 Nov;33(11):2324-34.
Remedial operation for primary hyperparathyroidism.
Prescott JD, Udelsman R.
Department of Surgery, Yale University School of Medicine, 330 Cedar Street, New
Haven, CT 06520, USA.
BACKGROUND: Remedial surgery for patients with persistent or recurrent primary
hyperparathyroidism (1 degrees HPT) remains a significant challenge. Cervical
reexploration is technically difficult; reoperative neck anatomy is distorted by
fibrosis and, as a result, remedial 1 degrees HPT patients carry an increased
risk of injury to the recurrent (RLN) and superior laryngeal nerve(s) as well as
to normal residual parathyroid tissue. Causative hyperfunctioning parathyroid
tissue is also more frequently ectopic in the remedial setting and can thus be
difficult to localize.
METHODS: This report assimilates the current data underlying preoperative,
intraoperative and postoperative remedial 1 degrees HPT management and presents
an evidence-based algorithm for the management of remedial parathyroid disease.
Recommendations are graded according to the quality of supporting data using the
system initially developed by Sackett (Chest 95:2S-4S, 1989) and subsequently
modified by Heinrich et al. (Ann Surg 243:154-168, 2006).
RESULTS: Recent advances in preoperative localization and intraoperative adjuncts
have lead to substantial improvements in outcomes after remedial surgery.
Preoperative localization techniques, including sestamibi scintigraphy (MIBI),
high resolution ultrasound (US), US-guided fine needle aspiration (FNA) and
selective venous sampling (SVS), coupled with intraoperative adjuncts such as the
rapid parathyroid hormone (PTH) assay have lead to reoperative cure rates as high
as 96 percent. Nonetheless, management of remedial 1 degrees HPT varies
significantly between surgeons and no formal recommendations standardizing the
care of these patients have been published.
CONCLUSIONS: Despite the significant challenges associated with remedial surgery
for 1 degrees HPT, excellent outcomes can be reproducibly achieved when proper
pre-, intra-, and postoperative management is employed.
World J Surg. 2009 Nov;33(11):2335-42.
Surgical and medical treatment of secondary hyperparathyroidism in patients on
continuous dialysis.
Tominaga Y, Matsuoka S, Uno N.
Department of Transplant and Endocrine Surgery, Nagoya Second Red Cross Hospital,
2-9, Myoken-cho, Showa-ku, Nagoya 4668650, Japan. ytomi@nagoya2.jrc.or.jp
BACKGROUND: Secondary hyperparathyroidsm (2HPT) is a common complication in
hemodialysis patients associated with morbidity and sometimes mortality. The
majority of patients with 2HPT can be managed by medical treatment. However,
medical treatment does not always provide control of parathyroid disorder. Some
patients require surgical treatment, parathyroidectomy (PTx). Successful surgical
treatment often results in dramatic drop of the parathyroid hormone (PTH) levels,
relieves the patients from clinical symptoms, and reduces mortality. However, at
present we do not have reliable evidences showing that PTx.
METHODS: The published papers about medical and surgical treatment for 2HPT
within the last 10 years were evaluated to acquire the evidence for the adequate
surgical treatments for 2HPT.
RESULTS: Many retrospective, observation studies have confirmed that successful
PTx can achieve a dramatic drop of PTH levels, relieve symptoms of 2HPT and
reduce mortality. However, we do not have reliable evidence that PTx compared
with placebo or active drugs, improves mortality or outcome with respect to
cardiovascular symptoms, bone disease, or biochemical parameter. The indications
for surgery may be strongly influenced by medical therapy, including treatment
with calcimimetics, as well as by composition of the patients material and
medical insurance system. There are many treatment of modalities in addition to
PTx for dialysis patients with 2HPT. Moreover, we do not have clear evidence
telling us which operative procedures is most appropriate for 2HPT, with respect
to clinical effectiveness, mortality or risk for recurrence.
CONCLUSION: To acquire the evidence for the adequate medical and surgical
treatment for 2HPT including operative procedures, randomized controlled
prospective studies are requires.
Ann Surg. 2008 Jul;248(1):18-30.
Surgical treatment of persistent hyperparathyroidism after renal transplantation.
Triponez F, Clark OH, Vanrenthergem Y, Evenepoel P.
Department of Thoracic and Endocrine Surgery, University Hospital of Geneva,
Geneva, Switzerland. frederic.triponez@hcuge.ch
OBJECTIVE: To provide a review on current knowledge about the pathogenesis,
epidemiology, and clinical complications of persistent hyperparathyroidism after
kidney transplantation (3HPT) and to discuss the surgical approaches.
BACKGROUND: 3HPT usually regresses within the first months after transplantation.
Parathyroidectomy for 3HPT is therefore not usually needed. Consequently, few
studies have been published regarding the best medical management for 3HPT and
indications for parathyroidectomy.
METHODS: Medical literature databases were searched for studies on the surgical
treatment of 3HPT published in English.
RESULTS: Forty-one studies were identified and included in this review.
CONCLUSIONS: 3HPT most commonly occurs in patients who have severe secondary
hyperparathyroidism at the time of transplantation. Indications for
parathyroidectomy in patients with 3HPT include persistent severe hypercalcemia,
defined as a serum calcium level greater than 11.5 mg/dl, unexplained renal
function deterioration, or progressive bone mineral density loss. Published
studies suggest that the best surgical approach for patients with 3HPT is
subtotal parathyroidectomy or total parathyroidectomy with autotransplantation.
3HPT poses important health risks, particularly concerning bone density and the
cardiovascular system. Because spontaneous improvement of parathyroid function is
uncommon after 3 months of transplantation, waiting for more than 6 months before
parathyroidectomy should be discouraged.
