Case Of Tertiary Hyperparathyroidism Research Articles

The role of calcium sensitive and vitamin D receptors in the pathogenesis of sporadic multiple parathyroid gland disease

Sporadic multiple parathyroid gland disease is ¼ cases of primary hyperparathyroidism (PHPT). However, a single tactic for diagnosing and operating volume in patients with this variant of PHPT has not yet been developed. One of the possible directions in the search for pathogenetically substantiated methods of diagnosis and treatment is the study of the molecular genetic features of the disease and associated clinical and laboratory factors. To study the features of the expression of calcium sensitive (CaSR) and vitamin D (VDR) receptors on the surface of parathyroid cells in primary hyperparathyroidism with solitary and multiple lesions of the parathyroid glands, as well as its changes under the influence of a decrease in the filtration function of the kidneys. In a single center observational prospective study with retrospective data collection, there were patients who during 2019-2021. operated on for PHPT, secondary hyperparathyroidism (SHPT) and all cases of tertiary hyperparathyroidism (THPT) operated during 2014-2021. The expression of CaSR, VDR and its relationship with the main laboratory parameters, the clinical variant of hyperparathyroidism, and the morphological substrate were studied. The study included 69 patients: 19 with multiple and 25 with solitary PTG near PHPT, 15 with SHPT, 10 with THPT. A statistically significant decrease in the frequency of detection of normal expression of CaSR and VDR receptors occurs in any morphological variant of hyperparathyroidism and is observed in 93-60% of drugs. A decrease in the normal expression of CaSR in hyperplasia is detected statistically significantly less frequently than in adenoma (p≤0.01). The median expression intensity in adenoma was 2.5 (2:3), in hyperplasia 3.5 (3-4) (p≤0.01). The difference in the molecular mechanisms of the development of hyperparathyroidism with a predominance of a morphological substrate in the form of adenoma (PHPT with solitary adenoma) or hyperplasia (SHPT and PHPT with multiple PTG lesions) is realized in the frequency of maintaining normal CaSR expression in the PTG tissue. These mechanisms are implemented at the local level, their variability does not change under the influence of RRT. A common molecular genetic mechanism for the development of hyperparathyroidism with a predominance of a morphological substrate in the form of adenoma or hyperplasia has been found to reduce the frequency of maintaining normal VDR expression in PTG (up to 7-13%), p<0.01. This mechanism is implemented at the local level, its variability changes under the influence of RRT, reaching statistically significant differences in patients with THPT. The study demonstrates the features of changes in the expression of CaSR and VDR in PHPT with multiple lesions of the parathyroid glands. The relationship between the expression of these receptors and the clinical variant of hyperparathyroidism, the morphological substrate, the main laboratory parameters, and renal function was shown.

MO802DOES ETELCALCETIDE REVERSE MYELOFIBROTIC BONE CHANGES DUE TO HYPERPARATHYROIDISM? A CASE REPORT

Abstract Background and Aims A 21 year old boy with a diagnosis of Autosomal Recessive Polycystic Kidney Disease and Caroli disease reached a final stage of chronic kidney disease (CKD) and started haemodialysis. Method After 3 years in haemodialysis he underwent a kidney transplant from a cadaveric donor. His transplanted kidney worked fairly well until the patients was 31 year old when he developed graft dysfunction (serum creatinine from 2.7 to 5 mg/dL in a very short period). There was a concomitant increase in serum phosphate levels (8.3 mg/dl) and iPTH that progressively increased to 1032 pg/ml despite a traditional therapy. Results At age 32, the patient returned to haemodialysis treatment thrice weekly with a concomitant a progressive worsening of hyperparathyroidism with bone pain . Cinacalcet at a dosage of 30 mg daily treatment was initiated, then it was increased to 120 mg daily without any benefit. Two years later, being the clinical situation without any improvement and being the patient scarcely compliant to the therapy and because a further enlargement of parathyroid glands was observed, a Parathyroidectomy (PTX) was advised. Nevertheless, PTX was not performed because of patient’s refusal. Furthermore, despite Erythropoietic Stimulating Agent (ESA) therapy, he developed severe anemia that required regular and frequent blood transfusions. iPTH increased to 4500 pg/ml [Fig.1] with a parallel rise in alkaline phosphatase >600 UI/L [Fig.2]. A Computed Tomography scan showed multiple bone-thickening lesions. He thus initiated Etelcalcetide 5 mg e.v. 3 times a week, after the HD session but without any benefit. The dosage was then increased to 7.5 mg but the patient gradually became frail and developed pancytopenia and low-grade fever. Hematological evaluation with bone marrow biopsy was performed in December 2019. Bone marrow histology showed severe fibrosis [Myelofibrosis (MF) grade 3] with normal bone marrow cytogenetics. Blood samples for mutations in JAK-2, CALR, and MPL and BCR-ABL rearrangement were negative. There was no evidence for a myeloproliferative neoplasm (MPN) or metastatic lesions. During the following months, while on a 7,5 mg dose of etalcalcetide, there was a gradual reduction in iPTH [Fig.1] and serum alkaline phosphatase [Fig.2], up to 500 pg/dl and 200 IU/L respectively. The patient developed asymptomatic, often severe, hypocalcemia which was managed with therapy. The patient’s clinical conditions gradually improved, anemia responded to lower doses of ESAs. A bone marrow biopsy was repeated after one year (December 2020) and it showed a reduction in fibrosis (MF grade varying from 1-2). Then etelcalcetide dosage was reduced while serum calcium and phosphate levels were in the normal limit. Conclusion Myelofibrosis secondary to renal osteodystrophy is an uncommon complication. It has been rarely reported and usually is associated with primary hyperparathyroidism. Marrow fibrosis and pancytopenia is related to the excessive iPTH that upregulates production of cytokines and paracrine factors in the bone marrow (IL-1a, IL-6, FNF-a, TGF–b, and platelet-derived growth factor) and it has an important stimulatory effect on fibroblast proliferation. It is known that surgical parathyroidectomy is associated with a reduction of bone marrow fibrosis in primary hyperparathyroidism. To our knowledge, this is probably the first case of tertiary hyperparathyroidism in which the effect of etelcalcetide is comparable to parathyroidectomy as far as on calcium-phosphate balance, and a significant improvement in bone marrow fibrosis and hemoglobin. In conclusion, etelcalcetide at least in this patient seems as effective as PTX on bone balance, bone marrow and anemia.

Paratiroidectomía transoral endoscópica por abordaje vestibular: experiencia inicial en la Argentina

Background: Different scenarios have emerged with the advent of minimally invasive approaches; transoral endoscopic parathyroidectomy vestibular approach (TOEPVA) is a technique with promising results.Objective: The aim of this study is to describe the surgical technique and the experience gained.Material and methods: We describe 3 patients with asymptomatic primary hyperparathyroidism due to parathyroid adenoma and one case of tertiary hyperparathyroidism with parathyroid hyperplasia with clinical signs and presence of lesions in imaging tests.Results: In 3 patients operative time was 202.5 minutes. The patients had adequate tolerance to pain and remained hospitalized for 24 hours. One patient with ectopic parathyroid adenoma required conversion to open surgery that was complicated with an accidental esophageal injury. Intraoperative parathormone levels decreased by >50% compared by baseline values in all the cases.Conclusions: This minimally invasive procedure is reproducible but should be used in selected cases as it is not free of complications.

A New Approach to Tertiary Hyperparathyroidism: Percutaneous Embolization: Two Case Reports

Secondary hyperparathyroidism is one of the most common complications of chronic kidney failure. If prolonged, parathyroid hormone release gains autonomy and tertiary hyperparathyroidism with parathyroid adenoma or hyperplasia can be develop. Tertiary hyperparathyroidism is associated with increased risk of mortality and morbidity; thus, treatment is recommended. Medical treatment includes phosphate binders, vitamin D analogues, and calcimimetic agents. Most cases of tertiary hyperparathyroidism can be controlled with medical treatment. When medical treatment options prove insufficient, parathyroidectomy is recommended. However, recurrence after parathyroidectomy is possible, which requires an alternative treatment. We present our percutaneous embolization experience, which has not been tried in the treatment of tertiary hyperparathyroidism in renal transplantation patients diagnosed with tertiary hyperparathyroidism.

Nuclear diameter in parathyroid disease.

The nuclear diameter of chief cells was measured in 17 cases of parathyroid adenomas, four cases of secondary hyperplasia, five cases of primary hyperplasia and six cases of tertiary hyperparathyroidism. All the cases with secondary hyperplasia and tertiary hyperparathyroidism were associated with chronic renal failure. The nuclear diameter in both the adenomatous and hyperplastic areas of tertiary hyperparathyroidism were measured. The adenomatous areas of tertiary hyperparathyroidism contained nuclei of a larger diameter than those in the hyperplastic foci of the same gland. The nuclear diameter in adenomatous foci of tertiary hyperparathyroidism was similar to that in adenomas from primary hyperparathyroidism. These findings lend support to the concept of formation of autonomous adenomas against a background of reactive parathyroid hyperplasia in cases of tertiary hyperparathyroidism. Using statistical methods there were differences between the nuclear diameter in cases of primary adenomata, and cases of primary and secondary hyperplasia. Primary parathyroid hyperplasia stood out as a distinct group. The significance of these findings is discussed.