Absence Of Hyperparathyroidism Research Articles

Abstract 142: Endocrine neoplasia type 2B with a rare mutation: A case report

Introduction: Multiple Endocrine Neoplasia (MEN) type 2 is a rare familial endocrine syndrome. MEN 2B syndrome, the least common subtype of MEN 2 syndrome, is characterized by medullary carcinoma of thyroid (MTC), pheochromocytoma and absence of hyperparathyroidism. Identifying the responsible mutation have prognostic consequences. Majority of MEN2B cases occur due to de-novo mutation with 95% cases involving codon 918, and codon 883, 2-3% cases.Objective: Identification of the genetic mutation in patient presented with MTC, and bilateral adrenal pheochromocytoma.Methods: Whole Exome Analysis was performed to identify the genetic defect. The variants were prioritized using standard open-source computational pipelines.Results: Whole exome sequencing and computational analysis identified a non-synonymous single nucleotide polymorphism T1991C in the exon 13 of RET gene on chromosome 10, resulting in a missense mutation (p.M664T) in the protein responsible for phenotypic expression known as MEN 2B syndrome.Conclusion: MTC and bilateral pheochromocytoma are indications for detailed clinical and genetic examination of the proband. Bilateral adrenalectomy, followed by total thyroidectomy and prophylactic central neck dissection was done along with lifetime hormone supplementation. This is a rare mutation reported in MEN2B (A Rare Syndrome) which usually involve codon 918 and 883.

Secondary hyperparathyroidism and its relationship with sarcopenia in elderly women

Low dietary intake of calcium and poor vitamin D status during aging can result in mild secondary hyperparathyroidism, which may be associated with low muscle mass and reduced strength in the elderly. The aim of this study was to investigate whether low vitamin D, high parathormone (PTH), or both, are associated with sarcopenia. A total of 105 women, 35 with sarcopenia and 70 without sarcopenia, were enrolled in the present study. Body composition measurements were performed by DXA and sarcopenia was defined as skeletal muscle mass index<5.45kg/m2 and grip strength lower than 20kg. Three-day dietary records were taken and adjustments for energy intake made. The estimated average requirement (EAR) method was adopted as a cut-off point for estimating the prevalence of inadequate intake. Serum total calcium, phosphorus, creatinine, intact PTH, and 25(OH)D were measured. Only 1% of the patients met the daily adequate intake for vitamin D and 11% met the daily adequate intake for calcium. Notably, the prevalence of sarcopenia was higher in hyperparathyroidism (25(OH)D<20ng/mL and PTH>65pg/dL) than in the absence of hyperparathyroidism (41.2 vs 16.2%, respectively; p=0.046). The odds ratio for sarcopenia in hyperparathyroidism cases was 6.81 (95%CI 1.29–35.9) compared with participants who had low PTH and a high 25(OH)D concentration. The present study showed that vitamin D insufficiency associated with secondary hyperparathyroidism increased the risk of sarcopenia, suggesting that the suppression of hyperparathyroidism by ensuring adequate calcium and vitamin D intake should be considered in interventional studies to confirm potential benefits.

OC1 Bilateral central giant cell granuloma of the mandible: a case report

Central giant cell granuloma (CGCG) is a benign lesion of unknown etiology that especially affects the jaws, usually appears in patients younger than 30 years and is more common in females than in males. Lesions generally occur in the anterior portion of the jaws and mandibular lesions frequently cross the midline. The conventional treatment of CGCG is surgical removal. According to clinical and radiological features, the extent of tissue removal ranges from simple curettage to an en bloc resection. We present an 8‐year‐old male patient, lack of any systemic disease or syndrome, complaining from painless swelling of the left posterior part of the mandible. In intraoral examination, a firm, expansive swelling with overlying intact mucosa, extending from mandibular primary canine to the distal portion of the left permanent first molar, was detected. A panoramic radiograph exhibited an ill‐defined radiolucent lesion of 1.5 x 2 cm, extending from left permanent first molar to angulus mandibula and a well‐defined, unilocular radiolucent lesion of 1 x 2 cm, extending from angulus to ramus mandibula on the asymptomatic right side. After the assessment of MRI, surgical removal was planned with the otorhinolaryngology department and lesions were totally removed under general anesthesia in two consecutive operation. Histopathologic examination revealed typical giant cell granuloma containing numerous multinucleated giant cells embedded in a fibrous stroma. In presenting this case we aimed to share occurrence of bilateral central giant cell granulomas of the mandible in the absence of hyperparathyroidism and associated syndromes, which is very rare in the literature.

RETProto-Oncogene: A Review and Update of Genotype–Phenotype Correlations in Hereditary Medullary Thyroid Cancer and Associated Endocrine Tumors

Hereditary medullary thyroid carcinoma (MTC) is caused by autosomal dominant gain-of-function mutations in the RET proto-oncogene. Associations between specific RET mutations (genotype) and the aggressiveness of MTC and presence or absence of other endocrine neoplasms (phenotype) are well documented. Mutations in six exons (10, 11, 13, 14, 15, and 16) located in either cysteine-rich or tyrosine kinase domains cause one of three distinctive clinical subtypes: familial MTC, multiple endocrine neoplasia (MEN) type 2A (including variants with Hirschsprung's disease and cutaneous lichen amyloidosis), and MEN 2B. Hallmarks of MEN 2A include MTC, pheochromocytoma, and hyperparathyroidism. MEN 2B is associated with an earlier onset of MTC and pheochromocytoma, the absence of hyperparathyroidism, and the presence of striking physical stigmata (e.g., coarse facies, ganglioneuromatosis, and marfanoid habitus). Familial MTC is not associated with other endocrine neoplasms; however, the accurate distinction between familial MTC and MEN 2A may be difficult in kindreds with small size, incomplete histories, or a predominance of young individuals who may not have yet fully manifested the syndrome. Genetic testing detects greater than 95% of mutation carriers and is considered the standard of care for all first-degree relatives of patients with newly diagnosed MTC. Recommendations on the timing of prophylactic thyroidectomy and the extent of surgery are based upon a model that utilizes genotype- phenotype correlations to stratify mutations into three risk levels.

Successful treatment of an adynamic bone disorder with bone morphogenetic protein-7 in a renal ablation model.

An adynamic bone disorder (ABD) is an important complication of chronic kidney disease (CKD) of unknown etiology for which there is no adequate treatment. Reported is an animal model of ablative CKD complicated by an ABD characterized by the absence of secondary hyperparathyroidism and its successful treatment with a skeletal anabolic factor, bone morphogenetic protein-7 (BMP-7). Adult mice were subjected to electrocautery of the right kidney followed by left nephrectomy. Animals were randomized into groups fed normal chow or fed low-phosphate chow supplemented with calcitriol to maintain normophosphatemia in CKD. All groups were maintained on the regimens for 12 wk. Hyperphosphatemia, secondary hyperparathyroidism, and a mild osteodystrophy developed in the CKD/chow-fed group, as expected. When dietary phosphorus was restricted and calcitriol was administered in the CKD low-phosphate/calcitriol group (ABD), Ca, PO(4), and parathyroid hormone levels were maintained normal. A significant ABD developed in the ABD group characterized by significant depressions in osteoblast number, perimeters, bone formation rates, and mineral apposition rates when compared with the sham-operated, chow-fed group. The abnormal skeletal histomorphometry was reversed by BMP-7 therapy to normal values and significantly improved from the ABD group (P < 0.05). The sham-operated low-phosphate/calcitriol-fed control group and the CKD low-phosphate/calcitriol/BMP-7 groups had reduced phosphate levels compared with the other groups (P < 0.05). ABD produced in mice with CKD in the absence of hyperparathyroidism was successfully reversed with a bone anabolic, BMP-7, associated with a reduction in plasma phosphorus.

Dietary content may prevent secondary hyperparathyroidism in female rhesus monkeys (Macaca mulatta).

Macaque laboratory chows provide relatively more calcium (Ca) and vitamin D (D) than human diets; this may influence skeletal aging. To evaluate this possibility, parameters of skeletal relevance in premenopausal and naturally postmenopausal rhesus monkeys were measured in a cross-sectional study. Serum osteocalcin (Oc) was elevated in the postmenopausal group (P < 0.01), but levels of parathyroid hormone (PTH) and 25-hydroxyvitamin D (25OHD) were not different. Subsequently, in premenopausal animals, dietary Ca and/or D intake was reduced to optimal human levels for 8 weeks prior to the evaluation of the skeletal parameters. Serum 25OHD concentration was reduced (P < 0.01) and a trend (P=0.10) towards increased PTH was observed in both low D groups. In addition, serum alkaline phosphatase (ALP) levels were increased in the low Ca group (P < 0.01). In conclusion, skeletal turnover, as measured by serum Oc, was increased in naturally postmenopausal rhesus monkeys in the absence of hyperparathyroidism. Dietary D reduction causes a decline in serum 25OHD and an upward trend in PTH.

Sodium Thiosulfate in the Treatment of Tumoral Calcifications in a Hemodialysis Patient without Hyperparathyroidism

Extraskeletal tumoral calcifications (TC) may occur in patients with end-stage renal disease. The TC usually develop in the presence of secondary hyperparathyroidism or a high calcium x phosphate product, while other factors have been also occasionally implicated in their development. At present, no uniformly accepted effective treatment has been described for this condition. We describe a 58-year-old female patient with end-stage renal disease who 7 years after the onset of dialysis presented with pain and movement restriction of various joints. A skeletal X-ray showed huge amounts of periarticular TC. The TC occurred in the absence of hyperparathyroidism or a high calcium x phosphate product as evidenced by hormonal and biochemical examination as well as by a bone biopsy specimen that revealed an adynamic bone disease with significant aluminum staining. Sodium thiosulfate, an inorganic salt that has been claimed to inhibit the formation and to favor the solubility and the mobilization of calcified masses, was administered to the patient, and after a long period of treatment considerable radiological regression of the TC with concurrent clinical recovery was noticed. Aluminum intoxication, along with other factors, was considered to be the cause of TC development. The use of sodium thiosulfate seemed to be a reasonable nonspecific therapeutic approach for the management of TC in this case.

Absence of hyperparathyroidism in severe liver disease

Elevated serum levels of intact parathyroid hormone (PTH) have been reported in severe versus mild biliary cirrhosis. The aim of this study was to determine whether hyperparathyroidism was present in severe liver disease on the basis of the inability of the liver to catabolize the hormone. Because biologic activity resides in the amino terminal, and amino terminal PTH determinations have not been routinely made in liver disease, it is possible that hyperparathyroidism was previously missed in these patients. Accordingly, we obtained fasting blood from 11 patients with severe liver disease and 8 age-matched controls. We measured intact, amino terminal, and mid-region PTH, vitamin D metabolites, bone gamma carboxyglutamic acid protein (BGP), ionized calcium, phosphorus, magnesium, and liver function tests. Serum levels of PTH were normal with all assays and 1,25(OH)2D levels were not elevated. These findings argue against the possibility that hyperparathyroidism plays a role in the pathogenesis of hepatic osteodystrophy.

Hypophosphatemic osteomalacia and adult fanconi syndrome due to light-chain nephropathy: Another form of oncogenous osteomalacia

Two patients, one with myeloma (Patient 1) and the other with probable chronic lymphocytic leukemia (Patient 2), had reduced renal tubular phosphate reabsorption in the absence of hyperparathyroidism together with other features of the Fanconi syndrome, as consequences of the nephropathy associated with light-chain proteinuria. Both patients had hypophosphatemic osteomalacia, demonstrated for the first time in this condition by iliac bone histomorphometry after in vivo double tetracycline labeling, despite absence of bone pain or Looser zones. Neither patient was vitamin D-depleted, but plasma calcitriol level was normal in Patient 1 and low in Patient 2; only the latter patient had severe muscle weakness. Complete histologic correction of osteomalacia was achieved by treatment in accordance with the biochemical defects—oral phosphate therapy alone in Patient 1 and combined with calcitriol in Patient 2. Both patients are now symptom-free, five and three years after the initial diagnosis of bone disease and hematogenous malignancy. Thirteen previous instances of the same form of osteomalacia were reviewed; in most cases, the Fanconi syndrome developed before its probable cause became apparent. The Fanconi syndrome has also been reported in two cases of osteomalacia due to mesenchymal tumor, but not in osteomalacia associated with prostatic carcinoma. Light-chain nephropathy and consequent renal tubular dysfunction appears to be a third form of oncogenous osteomalacia.