The Parathyroids

Secondary Hyperparathyroidism ◽

Calcium Homeostasis ◽

Laryngeal Nerve ◽

Parathyroid Glands ◽

Tertiary Hyperparathyroidism ◽

Endocrine Neoplasia ◽

And Function

Successful surgery of the parathyroid glands depends on a thorough knowledge of their anatomic and developmental relations. This knowledge is crucial for locating ectopic parathyroids or preventing injury to the recurrent laryngeal nerve. In addition, the surgeon should understand the physiology and function of these glands. Unlike other conditions a surgeon might treat, physiology, and not anatomy alone, often dictates the timing and course of parathyroid procedures. This surgeon-oriented, focused review covers the development, histology, anatomy, physiology, and pathophysiology of the parathyroid. Figures show the location and frequencies of ectopic upper and lower parathyroid glands, and regulation of calcium homeostasis. This review contains 2 highly rendered figures, and 16 references Key words: calcitonin; hypercalcemia; hyperparathyroidism; multiple endocrine neoplasia; parathyroid; parathyroid hormone; primary hyperparathyroidism; secondary hyperparathyroidism; tertiary hyperparathyroidism

Relationship between parathyroid calcium-sensing receptor expression and potency of the calcimimetic, cinacalcet, in suppressing parathyroid hormone secretion in an in vivo murine model of primary hyperparathyroidism

Acta Endocrinologica ◽

10.1530/eje.1.02007 ◽

2005 ◽

Vol 153 (4) ◽

pp. 587-594 ◽

Cited By ~ 28

Author(s):

Takehisa Kawata ◽

Yasuo Imanishi ◽

Keisuke Kobayashi ◽

Takao Kenko ◽

Michihito Wada ◽

...

Keyword(s):

Parathyroid Hormone ◽

Secondary Hyperparathyroidism ◽

Murine Model ◽

Hormone Secretion ◽

Suppressive Effect ◽

Receptor Expression ◽

Parathyroid Glands ◽

Calcium Sensing Receptor ◽

Calcium Sensing

Cinacalcet HCl, an allosteric modulator of the calcium-sensing receptor (CaR), has recently been approved for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis, due to its suppressive effect on parathyroid hormone (PTH) secretion. Although cinacalcet’s effects in patients with primary and secondary hyperparathyroidism have been reported, the crucial relationship between the effect of calcimimetics and CaR expression on the parathyroid glands requires better understanding. To investigate its suppressive effect on PTH secretion in primary hyperparathyroidism, in which hypercalcemia may already have stimulated considerable CaR activity, we investigated the effect of cinacalcet HCl on PTH-cyclin D1 transgenic mice (PC2 mice), a model of primary hyperparathyroidism with hypo-expression of CaR on their parathyroid glands. A single administration of 30 mg/kg body weight (BW) of cinacalcet HCl significantly suppressed serum calcium (Ca) levels 2 h after administration in 65- to 85-week-old PC2 mice with chronic biochemical hyperparathyroidism. The percentage reduction in serum PTH was significantly correlated with CaR hypo-expression in the parathyroid glands. In older PC2 mice (93–99 weeks old) with advanced hyperparathyroidism, serum Ca and PTH levels were not suppressed by 30 mg cinacalcet HCl/kg. However, serum Ca and PTH levels were significantly suppressed by 100 mg/kg of cinacalcet HCl, suggesting that higher doses of this compound could overcome severe hyperparathyroidism. To conclude, cinacalcet HCl demonstrated potency in a murine model of primary hyperparathyroidism in spite of any presumed endogenous CaR activation by hypercalcemia and hypo-expression of CaR in the parathyroid glands.

Failure of Cimetidine to Affect Calcium Homeostasis in Familial Primary Hyperparathyroidism (Multiple Endocrine Neoplasia, Type 1)*

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem-51-4-912 ◽

1980 ◽

Vol 51 (4) ◽

pp. 912-914 ◽

Cited By ~ 14

Author(s):

MICHAEL F. ROBINSON ◽

ALVIN B. HAYLES ◽

HUNTER HEATH

Keyword(s):

Calcium Homeostasis ◽

Familial Primary Hyperparathyroidism

Endocrine Neoplasia ◽

Endocrine Neoplasia Type ◽

Parathyroid hormone release in vitro in hyperparathyroidism associated with multiple endocrine neoplasia type 1

Acta Endocrinologica ◽

10.1530/acta.0.1140012 ◽

1987 ◽

Vol 114 (1) ◽

pp. 12-17 ◽

Cited By ~ 9

Author(s):

Lars Benson ◽

Jonas Rastad ◽

Sverker Ljunghall ◽

Claes Rudberg ◽

Göran Åkerström

Keyword(s):

Parathyroid Hormone ◽

Parathyroid Glands ◽

Men 1 ◽

Endocrine Neoplasia ◽

Parathyroid Adenomas ◽

Patient Groups

Abstract. Hyperparathyroidism (HPT) in the syndrome of multiple endocrine neoplasia type 1 (MEN-1) exhibits a different picture regarding its propensity for recurrence compared with sporadic primary HPT. In order to shed further light on the MEN-1 syndrome an investigation in vitro was made of parathyroid hormone (PTH) release of dispersed parathyroid cell from 11 patients with parathyroid hyperplasia associated with MEN-1, 10 patients with single parathyroid adenomas, and 10 preparations of normal bovine parathyroid glands. The two patient groups had the same average serum calcium value prior to surgery. Immunoreactive concentrations of PTH were measured after 2-h incubations at extracellular calcium concentrations of 0.5–3.0 mmol/l. Compared with the normal bovine parathyroid cells, the cells of the MEN-1 patients had a reduced calcium sensitivity of the PTH release and secreted smaller amounts of hormone at both low and high extracellular calcium concentrations. A similar abnormality of the PTH release was found for the cells of the hyperplastic and adenomatous parathyroid glands. Although individual parathyroid glands were investigated in only three MEN-1 patients, the results suggested the secretory regulation to be less defective in the small glands of each patient. It is concluded that in patient groups matched for serum calcium, the parathyroid tissue of MEN-1 patients has an abnormality of the PTH release similar to that of parathyroid adenomas.

Familial isolated primary hyperparathyroidism--a multiple endocrine neoplasia type 1 variant?

Acta Endocrinologica ◽

10.1530/eje.0.1450155 ◽

2001 ◽

pp. 155-160 ◽

Cited By ~ 35

Author(s):

S Miedlich ◽

T Lohmann ◽

U Schneyer ◽

P Lamesch ◽

R Paschke

Keyword(s):

Parathyroid Hormone ◽

Family Members ◽

Statistical Comparison ◽

Men1 Gene ◽

Men 1 ◽

Endocrine Neoplasia

OBJECTIVE: Familial isolated primary hyperparathyroidism (FIHP) is defined as hereditary primary hyperparathyroidism without the association of other diseases or tumors. Linkage analyses suggest that different genotypes can lead to the same phenotype of primary hyperparathyroidism. Hereditary syndromes associated with primary hyperparathyroidism are multiple endocrine neoplasia type 1 and type 2 (MEN 1 and MEN 2). In MEN 1, multiple parathyroid adenomas occur in more than 90% of the patients. Therefore, it has been suggested that FIHP could represent a variant or partial expression of MEN 1. DESIGN: We report on a large FIHP kindred with a MEN1 gene mutation. Nineteen family members (aged 10 to 87 years) were screened. Furthermore, statistical comparison by Fisher's exact tests of FIHP families with MEN1 gene mutations and MEN 1 families with two or more endocrinopathies was carried out to investigate genotype-phenotype correlations. METHODS: Mutational analysis of leucocyte DNA was carried out by direct sequencing of the complete coding region of the MEN1 gene. Screening of MEN 1 manifestations was carried out by determination of serum calcium, phosphate, parathyroid hormone, prolactin, ACTH, cortisol, IGF-I, gastrin, glucose, insulin, glucagon, serum potassium, aldosterone, plasma renin and urinary hydroxyindoleacetic acid. RESULTS: We detected an in-frame deletion mutation in exon 8 of the MEN1 gene resulting in the deletion of one glutamine acid residue at position 363. It was found in eight individuals. Two of these family members (aged 42 and 60 years) were operated for primary hyperparathyroidism, and three (aged 13 to 40 years) showed mild hypercalcemia and parathyroid hormone levels within the upper normal range or slightly elevated, without any clinical symptoms. Two individuals (aged 12 and 19 years) were normocalcemic. One could not be tested. None of them had clinical evidence of other MEN 1 manifestations. Statistical comparison of the mutation types in families with FIHP and families with two or more MEN 1-associated endocrinopathies reported in other studies reveals a significant difference. In families with FIHP, missense/in-frame mutations have been found in 87.5% of cases whereas in families with tumors in various endocrine glands these mutation types occur much less frequently (21-34%, P<0.05). CONCLUSIONS: These studies indicate that FIHP can represent a partial MEN 1 variant and is often caused by missense/in-frame mutations.

Utility of Intraoperative Parathyroid Hormone Monitoring in Patients with Multiple Endocrine Neoplasia Type 1-Associated Primary Hyperparathyroidism Undergoing Initial Parathyroidectomy

World Journal of Surgery ◽

10.1007/s00268-013-2054-1 ◽

2013 ◽

Vol 37 (8) ◽

pp. 1966-1972 ◽

Cited By ~ 20

Author(s):

Naris Nilubol ◽

Allison B. Weisbrod ◽

Lee S. Weinstein ◽

William F. Simonds ◽

Robert T. Jensen ◽

...

Keyword(s):

Parathyroid Hormone ◽

Intraoperative Parathyroid Hormone

Endocrine Neoplasia ◽

Endocrine Neoplasia Type ◽

Parathyroid Hormone Monitoring ◽

Calcium and Bone Metabolism Disorders

Mayo Clinic Internal Medicine Board Review ◽

10.1093/med/9780190464868.003.0012 ◽

2016 ◽

pp. 149-156

Author(s):

Marius N. Stan

Keyword(s):

Parathyroid Hormone ◽

Parathyroid Carcinoma ◽

Multiglandular Disease ◽

Common Cause ◽

Endocrine Neoplasia ◽

Familial Hyperparathyroidism

The causes of hypercalcemia are categorized as either parathyroid hormone (PTH) dependent or PTH independent. Primary hyperparathyroidism is the most common cause of hypercalcemia in ambulatory patients. A single parathyroid adenoma is the cause in 85% of patients, and multiglandular disease is the cause in the remainder. Parathyroid carcinoma is a rare cause of hypercalcemia. Primary hyperparathyroidism may be sporadic or familial. Familial hyperparathyroidism is usually multiglandular and most commonly a manifestation of multiple endocrine neoplasia (MEN) type 1 or type 2 syndromes.

Multiglandular Parathyroid Disease: the Results of Surgical Treatment

Acta biomedica scientifica ◽

10.29413/abs.2020-5.4.13 ◽

2020 ◽

Vol 5 (4) ◽

pp. 90-97

Author(s):

E. A. Ilyicheva ◽

G. A. Bersenev ◽

A. V. Zharkaya ◽

D. A. Bulgatov ◽

V. N. Makhutov

Keyword(s):

Parathyroid Hormone ◽

Surgical Treatment ◽

Secondary Hyperparathyroidism ◽

Intraoperative Monitoring ◽

Parathyroid Glands ◽

Bilateral Neck Exploration ◽

Neck Exploration ◽

Multiple Lesions ◽

Multiple Gland Disease

Background. Sporadic multiple gland disease in primary hyperparathyroidism occurs in 7 to 33 % of cases. The absence of specific risk factors, low sensitivity of imaging methods, and low efficiency of bilateral neck exploration and intraoperative monitoring of parathyroid hormone indicate the complexity of the diagnosis and treatment of this disease’s form. Aim of the research. To analyze the results of surgical treatment of multiple lesions of the parathyroid gland in primary and secondary hyperparathyroidism. Methods. There was retrospective study, which included 100 observations of surgical treatment for primary and secondary hyperparathyroidism in the thoracic department of Irkutsk Regional Clinical Hospital from May 2018 to September 2019. The main point was to identify the frequency of surgical treatment outcomes in patients with multiple parathyroid lesions. As part of the study, potential predictors of multiple gland disease in primary hyperparathyroidism were analyzed. Results. Multiple gland disease in primary hyperparathyroidism occurs in 29 % of cases and causes persistence of the disease (p ≤ 0.01). Signs of multiple gland disease in primary hyperparathyroidism include the level of ionized calcium, parathyroid hormone (p ≤ 0.05), creatinine level and glomerular filtration rate (p ≤ 0.01). A negative result of intraoperative monitoring correlates with persistence of primary hyperparathyroidism in multiple lesions (χ2, p ≤ 0.05). Selective parathyroidectomy is associated with persistence of hyperparathyroidism in multiple lesions (χ2, p ≤ 0.05), while total parathyroidectomy is associated with remission of the disease (χ2, p ≤ 0.05). We did not find a statistically significant relationship between the results of surgical treatment for morphology of the parathyroid glands (χ2, p > 0.1). Conclusion. Multiple gland disease is the main cause of persistence of primary hyperparathyroidism. This form of the disease corresponds to lower levels of calcium, parathyroid hormone, and kidney function. Persistence factors have been established: removal of less than four parathyroid glands and a negative result of intraoperative monitoring of parathyroid hormone. Bilateral neck exploration does not reduce the incidence of disease persistence.