ACTA ENDOCRINOLOGICA (BUC)

Vitamin D deficiency and insufficiency are common medical problems worldwide as they\r\nare quite prevalent in both healthy adults and individuals with osteoporosis, hospitalized patients\r\nand free-living and institutionalized elderly. The lack of serum 25-hydroxy-vitamin D (25OHD)\r\nassays standardization, variability of reference population, and the use of different cut-off points\r\nhave produced quite different prevalence reports from epidemiological studies.\r\nWe investigated the vitamin D status (deficiency, insufficiency, sufficiency) in 1048\r\nRomanian postmenopausal women with osteoporosis referred to our clinic for diagnosis and\r\ntreatment in the last three years. Most patients were untreated with osteoporosis drugs and nonsupplemented\r\nwith vitamin D. In our country dietary sources of vitamin D are scarce and there\r\nis no fortification of food with vitamin D. We found a high prevalence of both vitamin D\r\ndeficiency (25OHD < 10 ng/mL) - 22.23% and insufficiency (25OHD=10-30 ng/mL) - 61.26%.\r\nOur study also revealed a high prevalence of low vitamin D when using other cut-offs as reported\r\nin the literature. 83.49% had values lower than 30 ng/mL and 60.97% lower than 20 ng/mL. In\r\nthis study we identified a serum 25OHD concentration of 35 ng/mL above which serum\r\nparathyroid hormone (PTH) concentration attains a plateau at about 35 pg/mL. The relation\r\nbetween serum PTH and 25OHD concentration was non-linear and a log-log diagram showed a\r\nvery weak correlation. The prevalence of secondary hyperparathyroidism was 32.25% in the\r\nwhole population studied. It ranged from 40% in the subgroup of serum 25OHD less than 10\r\nng/mL to less than 15% in patients with 25OHD higher than 30 ng/mL.\r\nIn conclusion, in a representative osteoporosis population from Romania we found a very\r\nhigh prevalence of vitamin D deficiency and insufficiency whatever the cut-off used for\r\ndefinition.

Primary bilateral adrenal lymphoma is a very rare cause of adrenal insufficiency. We report the case of a 63-year-old woman who presented with signs and symptoms of impending adrenal crisis when referred for evaluation of large bilateral adrenal masses diagnosed on a computed tomography scan two weeks prior. Based on a high clinical suspicion of adrenal insufficiency, patient was initiated on glucocorticoid and mineralocorticoid therapy prior to laboratory confirmation of adrenal insufficiency. After stabilizing the patient and excluding pheochromocytoma, we proceeded with adrenal biopsy that revealed a nongerminal center-type diffuse large B-cell lymphoma. Our patient was treated with R-CHOP chemotherapy, with good response after 3 cycles but eventually died after the fifth cycle from neurologic complications. This case highlights the notion that primary adrenal insufficiency should be considered in patients presenting with bilateral adrenal masses. Although primary adrenal lymphoma is a very rare adrenal malignancy it should be considered in patients presenting with bilateral rapidly growing adrenal tumors and primary adrenal insufficiency.

Prolonged target gland failure causes pituitary hyperplasia, but rarely, secondary hyperplasias develop into autonomous neoplasms. We report herein a rare example of gonadotroph adenoma arising in a patient with prolonged hypogonadism due to Klinefelter syndrome. A pituitary macroadenoma with suprasellar extension was discovered incidentally by magnetic resonance imaging (MRI), in search for the cause of chronic saliva retention. His pre-operative serum concentrations of both luteinizing hormone (LH) and mostly follicle-stimulating hormone (FSH) were distinctly higher than normal, as expected, but the levels decreased after complete removal of the tumor, suggesting partial secretion of gonadotropins by the tumor. The surgically removed tissue showed a typical pituitary adenoma with distinct immunoreactivity for FSH (intense, homogeneous) and LH (scattered). In the fragmented parts of adjacent gland tissue, no hormone producing cell hyperplasia or presence of gonadal deficiency cells were detectable. In conclusion, our case is the description of a rare example of gonadotropin producing pituitary adenoma (FSH and LH) with increased serum levels of both gonadotropins in a patient with untreated Klinefelter syndrome.

Context. Trabecular Bone Score (TBS) has been recently proposed as a good tool to investigate secondary osteoporosis. Objective. The aim of this study was to assess TBS from spine DXA images in patients with primary hyperparathyroidism (PHPT) and look at its correlates. Subjects and Methods. 153 patients, mean age 59.1 ± 12.1 yrs, females and males (10%), mean BMI 26.2 ± 4.8 kg/m2, mean serum calcium and PTH of 11.3 ± 1.2 mg/dL and 232 ± 329 pg/mL, respectively; 89% had osteoporosis/ osteopenia by LS DXA and 46% had renal involvement. There were 7.6% patients with vertebral fractures, 13.2% patients with nonvertebral fractures. TBS indices were derived from LS-DXA images and cutoff points used were those previously reported. Results. Mean TBS was in the partially degraded range (1.258 ± 0.115); 32% of patients had degraded microarchitecture (TBS ≤ 1.20), 51% had partially degraded microarchitecture (TBS > 1.20 and < 1.35) and 17% had normal TBS. TBS was significantly correlated with areal BMD both at the LS (r=0.544; p<0.001) and FN (r = 0.315; p < 0.001), and negatively with age (r= - 0.354; p < 0.001) and years since menopause - YSM (r = - 0.257, p = 0.005). Patients with vertebral fractures had mean values of TBS in the degraded range, significantly lower than those without vertebral fractures (1.173 ± 0.076 vs. 1.263 ± 0.115; p = 0.006). The presence of vertebral fracture was independently associated only with YSM (OR = 1.131, 95% CI = 0.032 – 0.214, p = 0.008) but not with TBS. Conclusions. In a cohort of symptomatic PHPT patients, including postmenopausal, premenopausal and male patients, we have shown that TBS was in the partially degraded range, but it was not independently associated with fractures.

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Background. The purpose of this study was to observe the effects of denosumab on bone mineral density (BMD), bone turnover markers and serum calcium in patients with primary hyperparathyroidism (PHPT) and osteoporosis. Methods. Seven consecutive patients with PHPT were administered a single subcutaneous injection of denosumab, 60 mg. The subjects were followed up to 6 months: serum calcium on days 1,3,7,14,30 and at 3 months and 6 months; serum intact parathyroid hormone (iPTH), C-telopeptide (CTX) and N-mid osteocalcin at baseline, 3 months and 6 months. BMD by DXA, at the femoral neck (FN) and lumbar spine (LS), were measured at baseline and at 6 months. Results. The patients (mean age= 69.8 yrs, range 62-81) had mild PHPT (mean total calcium = 10.8 mg/dL; mean PTH = 148.9 pg/mL); all had osteoporosis and four were currently treated with various bisphosphonates (BP). After 6 months mean LS BMD increased significantly by 4.5 % (p = 0.04) and mean FN BMD by 2.4% (p= 0.09 two-tailed; p = 0.047 one-tailed). Serum CTX decreased significantly by 90% at 3 months (p = 0.04), and by 48% at 6 months (p = 0.02); the similar changes for serum osteocalcin were 41% and 42% (p = 0.07, onetailed), respectively. In the first two weeks, serum total Ca variably decreased vs. baseline (0.5 to 2.8 mg/dL) in six out of seven patients. After 6 months mean total serum Ca nonsignificantly increased vs. baseline (11.4 mg/dL vs. 10.8 mg/dL, p = 0.1). Serum iPTH levels did not significantly change at both 3 and 6 months; after 6 months there was a trend toward decreased values (p = 0.03 onetailed). Conclusion. Denosumab increased BMD at both lumbar spine and femoral neck, and significantly decreased bone resorption in patients with PHPT. The effects on hypercalcemia were mild and transient, with a numerical increase after 6 months.

Context. Hyperparathyroidism-jaw tumour (HPTJT) syndrome is a rare autosomal dominant cause of familial hyperparathyroidism associated with ossifying fibromas (OF) of the maxillofacial bones and increased risk of parathyroid carcinoma, caused by inactivating germline mutation of the cell division cycle 73 (CDC73) gene. Objective. To report the first Romanian family with HPT-JT and genetic screening of CDC73 gene. Subjects and Methods. Mutational analysis of the CDC73 gene and genetic screening of the family of a proband with HPT-JT. Histological diagnosis of parathyroid tumors (WHO criteria) and immunohistochemistry (parafibromin) were performed. Results. Three of the six screened family members had evidence of PHPT and surgically proven parathyroid tumours. Two of the three affected members had parathyroid carcinomas and one had two parathyroid adenomas. Genetic screening of CDC73 gene revealed that 4 of 6 patients showed a heterozygous germline deletion of one nucleotide: c.128-IVS1+1 delG. All the three affected patients, resulted to be carriers of the CDC73 mutation, but each one bearing a different CDC73 polymorphism. Conclusions. We identified a new CDC73 germline mutation in a Romanian family of HPT-JT. Analysis of clinical phenotypes in the four mutated individuals confirmed the incomplete penetrance and the variable clinical expression of the disease.

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Background. Unexplained high bone mass (HBM) (Bone Mineral Density-BMD Z-score at the lumbar spine or hip of ≥+3.2 SD, or a combined spine and hip Z score ≥4 SD) after routine bone densitometry occurs with a prevalence of approximately 2 out of 1.000 and is currently believed to be a mild form of skeletal dysplasia (1). Results. We present the case of a patient with unexplained HBM (Z-scores at L3, L1-L4, total hip and radius total were +3, +2.7, +2 and +1.8, respectively) and concurrent symptomatic primay hyperparathyroidism (total serum calcium 11.9 mg/dL, serum Parathyroid Hormone - PTH 189.3 pg/mL) of long duration. There were no significant BMD changes at any skeletal site after the surgical cure of hyperparathyroidism. Testing for LRP (low density lipoprotein receptor-related proteins) 5 gene mutations was negative. Conclusions. We presented an unusual case of the association of a HBM with primary hyperparathyroidism with resistance to the catabolic action of PTH. In spite of the negative result of LRP5 testing we do believe that a mutation of a gene involved in the Wnt pathway in bone is responsible.

Background. Hip fractures are a major issue of public health as they are responsible for high morbidity, excess mortality and costs. There are differences in Europe and worldwide in the incidence rates of hip fractures and time trends, in the context of the population aging. Ten years ago, we characterized the incidence of hip fracture in Romania using data from the national hospital discharge register. Objective. This is the first Romanian study to assess the hip fracture incidence rates over a period of 11 years, between 2008 and 2018. Subjects and Methods. This analysis is a nationwide retrospective study on hospitals reporting primary DRG data on hip fracture, using a rigorous definition with both diagnostic and surgical procedure codes. The population aged 40+ was stratified in 5-year intervals and both the crude incidence rates and the adjusted incidence rates of hip fracture using standardization on age for the 2018 reference population were calculated in women and men. Results. From 2008 to 2018, the number of hip fractures rose by 53 % in women (from 7513 to 11512) and 22.4 % in men (from 4266 to 5220). Meanwhile, the Romanian population over 40 years increased by 12.5% in women and 14.2% in men. The crude incidence rate rose by 36.2% in women and 7.2% in men and the age-standardized incidence rates by 27.4% in women and 6% in men. These increases are mostly based on 85+ age populations’ changes. Conclusions. In Romania, the hip fractures incidence continues to grow throughout an 11-year-period, especially in women, representing an increasing burden for our society.