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Primary hyperparathyroidism is the most frequent manifestation of multiple endocrine neoplasia type 1 (MEN1) syndrome. Bone and renal complications are common. Surgery is the treatment of choice, but the best timing for surgery is controversial and predictors of persistence and recurrence are not well known. Our study describes the clinical characteristics and the surgical outcomes, after surgery and in the long term, of the patients with MEN1 and primary hyperparathyroidism included in the Spanish Registry of Multiple Endocrine Neoplasia, Pheochromocytomas and Paragangliomas (REGMEN). Eighty-nine patients (49 men and 40 women, 34.2 ± 13 years old) were included. Sixty-four out of the 89 underwent surgery: a total parathyroidectomy was done in 13 patients, a subtotal parathyroidectomy in 34 and a less than subtotal parathyroidectomy in 15. Remission rates were higher after a total or a subtotal parathyroidectomy than after a less than subtotal (3/4 and 20/22 vs 7/12, P < 0.05), without significant differences in permanent hypoparathyroidism (1/5, 9/23 and 0/11, N.S.). After a median follow-up of 111 months, 20 of the 41 operated patients with long-term follow-up had persistent or recurrent hyperparathyroidism. We did not find differences in disease-free survival rates between different techniques, patients with or without permanent hypoparathyroidism and patients with different mutated exons, but a second surgery was more frequent after a less than subtotal parathyroidectomy.
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Background
This study aimed to investigate the association of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis with osteoporosis in postmenopausal women and men over 50 years of age with type 2 diabetes (T2DM).
Methods
In this study, 1243 patients with T2DM (T2DM with coexistent NAFLD, n = 760; T2DM with no NAFLD, n = 483) were analysed. Non-invasive markers, NAFLD fibrosis score (NFS) and fibrosis index based on four factors (FIB-4), were applied to evaluate NAFLD fibrosis risk.
Results
There was no significant difference in bone mineral density (BMD) between the NAFLD group and the non-NAFLD group or between males and females after adjusting for age, BMI and gender. In postmenopausal women, there was an increased risk of osteoporosis (odds ratio (OR): 4.41, 95% CI: 1.04–18.70, P = 0.039) in the FIB-4 high risk group compared to the low risk group. Similarly, in women with high risk NFS, there was an increased risk of osteoporosis (OR: 5.98, 95% CI: 1.40–25.60, P = 0.043) compared to the low risk group. Among men over 50 years old, there was no significant difference in bone mineral density between the NAFLD group and the non-NAFLD group and no significant difference between bone mineral density and incidence of osteopenia or osteoporosis among those with different NAFLD fibrosis risk.
Conclusion
There was a significant association of high risk for NAFLD liver fibrosis with osteoporosis in postmenopausal diabetic women but not men. In clinical practice, gender-specific evaluation of osteoporosis is needed in patients with T2DM and coexistent NAFLD.
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Testosterone therapy is the cornerstone in the care of men with hypogonadism and transgender males. Gel and intramuscular injections are most frequently used and are registered and included in the international guidelines. The specific preparation should be selected according to the patient’s preference, cost, availability, and formulation-specific properties. As the majority of men with hypogonadism and transgender males require lifelong treatment with testosterone, it is important to utilize a regimen that is effective, safe, inexpensive, and convenient to use with optimal mimicking of the physiological situation. This systematic review reviews current literature on differences between the three most used testosterone preparations in adult men with hypogonadism and transgender males. Although it appeared hardly any comparative studies have been carried out, there are indications of differences between the preparations, for example, on the stability of testosterone levels, hematocrit, bone mineral density, and patient satisfaction. However, there are no studies on the effects of testosterone replacement on endpoints such as cardiovascular disease in relation to hematocrit or osteoporotic fractures in relation to bone mineral density. The effect of testosterone therapy on health-related quality of life is strongly underexposed in the reviewed studies, while this is a highly relevant outcome measure from a patient perspective. In conclusion, current recommendations on testosterone treatment appear to be based on data primarily from non-randomized clinical studies and observational studies. The availability of reliable comparative data between the different preparations will assist in the process of individual decision-making to choose the most suitable formula.
Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, China
Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, China
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Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, China
Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, China
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Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, China
Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, China
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Health Management Center, The Second Affiliated Hospital of Zhejiang Chinese Medicine University, Zhejiang, China
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Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, China
Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, China
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Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, China
Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, China
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Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, China
Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, China
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Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, China
Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, China
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The clinical presentation of primary hyperparathyroidism (PHPT) differs between patients from developed and developing countries. In China, the clinical pattern has changed over the past few decades. Our aim was to elucidate general changes in the clinical characteristics of PHPT from 2010 to 2021. We enrolled 343 patients with PHPT at the Qilu Hospital of Shandong University, Jinan, China, from January 2010 to May 2021, including both surgical and non-surgical patients. Patients were divided into two subgroups, 2010–2016 (group A, n = 152) and 2017–2021 (group B, n = 191), based on the time span. We compared clinical manifestations and laboratory result data between these two groups. The mean patient age was 52.59 ± 13.55 years, and the male-to-female ratio was 1:2.54. Of the 343 patients, 183 (53.35%) had symptomatic PHPT; bone pain, urolithiasis, and fatigue were the most common symptoms. Post-operative pathology showed that 96.20% of the patients had parathyroid adenoma, whereas 2.41% had parathyroid carcinoma. Great changes occurred between 2010 and 2021; the percentage of patients with asymptomatic PHPT (aPHPT) increased from 36.18% in group A to 54.97% in group B. Moreover, patients in group B showed significantly lower serum calcium, alkaline phosphatase, parathyroid hormone, and urinary phosphate levels but higher serum 25-hydroxyvitamin D levels than those in group A. Clinical presentations in group B were also milder. In conclusion, the clinical characteristics of Chinese PHPT patients changed dramatically from 2010 to 2021, with asymptomatic PHPT (aPHPT becoming the predominant type over the last 3 years.
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Hypercalcemic crisis is a severe but rare complication of primary hyperparathyroidism (PHPT), and data on denosumab treatment of patients with this disease is still very limited. The aim of this paper is to investigate the hypocalcemic effect of denosumab in PHPT patients with severe hypercalcemia when surgery should be delayed or is impossible for some reasons. We performed a retrospective study of 10 patients. The analysis included the use of biochemical markers of calcium-phosphorus metabolism, which were followed after the administration of 60 mg of denosumab. The trend to calcium reduction was already determined on the 3rd day after denosumab administration. In most cases the decrease in serum calcium level to the range of 2.8 mmol/L on average or lower was observed on the 7th day (P = 0.002). In addition to a significant increase in calcium levels we confirmed a significant increase in the estimated glomerular filtration rate on 7th day (P = 0.012). After that, seven patients underwent successful parathyroidectomy and achieved eucalcemia or hypocalcemia, one patient developed the recurrence of parathyroid cancer after initial surgery, while two patients with severe cardiovascular pathology refused surgery. Our study shows that denosumab is a useful tool in PHPT-associated hypercalcemia before surgery or if surgery is contraindicated.
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Department of Medical Genetics, Cambridge University, Cambridge, UK
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Primary hyperparathyroidism (pHPT) is a common endocrine disorder that can be cured by parathyroidectomy; patients unsuitable for surgery can be treated with cinacalcet. Availability of surgery may be reduced during COVID-19, and cinacalcet can be used as bridging therapy. In this single-centre retrospective analysis, we investigated the utility and safety of cinacalcet in patients with pHPT receiving cinacalcet between March 2019 and July 2020, including pre-parathyroidectomy bridging. We reviewed and summarised the published literature. Cinacalcet dosages were adjusted by endocrinologists to achieve target calcium < 2.70 mmol/L. Eighty-six patients were identified, with the most achieving target calcium (79.1%) with a mean dose of 39.4 mg/day (±17.1 mg/day) for a median duration of 35 weeks (1–178 weeks). Calcium was normalised in a median time of 5 weeks. The majority of patients commenced cinacalcet of 30 mg/day (78 patients) with the remainder at 60 mg/day (8 patients). Forty-seven patients commencing lower dose cinacalcet (30 mg/day) achieved target calcium without requiring 60 mg/day. Baseline PTH was significantly higher in patients requiring higher doses of cinacalcet. 18.6% of patients reported adverse reactions and 4.7% discontinued cinacalcet. Patients treated with cinacalcet pre-parathyroidectomy required a higher dose and fewer achieved target calcium compared to medical treatment with cinacalcet alone. Post-operative calcium was similar to patients who were not given pre-parathyroidectomy cinacalcet. In summary, cinacalcet at an initial dose of 30 mg/day is safe and useful for achieving target calcium in patients with symptomatic or severe hypercalcaemia in pHPT, including those treated for pre-parathyroidectomy. We propose a PTH threshold of >30 pmol/L to initiate at a higher dose of 60 mg/day.
Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon, USA
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA
Department of Physiology & Pharmacology, Oregon Health & Science University, Portland, Oregon, USA
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Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon, USA
Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, Oregon, USA
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Like women, old female rhesus macaques undergo menopause and show many of the same age-associated changes, including perturbed activity/rest cycles and altered circulating levels of many hormones. Previous studies showed that administration of an estrogen agonist increased activity in female monkeys, that hormone therapy (HT) increased activity in postmenopausal women and that obesity decreased activity in women. The present study sought to determine if postmenopausal activity and circulating hormone levels also respond to HT when monkeys are fed a high-fat, high-sugar Western style diet (WSD). Old female rhesus macaques were ovo-hysterectomized (OvH) to induce surgical menopause and fed a WSD for 2 years. Half of the animals received estradiol-17β (E), beginning immediately after OvH, while the other half received placebo. Animals in both groups showed an increase in body weight and a decrease in overall activity levels. These changes were associated with a rise in both daytime and nocturnal serum leptin concentrations, but there was no change in serum concentrations of either cortisol or dehydroepiandrosterone sulfate (DHEAS). These data suggest that 2 years of HT has little or no effect on locomotor activity or circadian hormone patterns in menopausal macaques fed an obesogenic diet.
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Objective
Parathyroid carcinoma is a rare tumor among parathyroid tumors. Aspiration cytology and needle biopsy are generally not recommended for diagnostic purposes because they cause dissemination. Therefore, it is commonly diagnosed by postoperative histopathological examination. In this study, we investigated whether preoperative inflammatory markers can be used as predictors of cancer in patients with primary hyperparathyroidism.
Design
This was a retrospective study.
Methods
Thirty-six cases of parathyroid carcinoma and 50 cases of parathyroid adenoma (PA) operated with the diagnosis of primary hyperparathyroidism and confirmed histopathologically at Ito Hospital were included in this study. Preoperative clinical characteristics and inflammatory markers (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio (LMR)) were compared and their values in preoperative prediction were evaluated and analyzed.
Results
Preoperative intact-parathyroid hormone (P = 0.0003), serum calcium (P = 0.0048), and tumor diameter (P = 0.0002) were significantly higher in parathyroid carcinoma than in PA. LMR showed a significant decrease in parathyroid carcinoma (P = 0.0062). In multivariate analysis, LMR and tumor length diameter were independent predictors. In the receiver operating characteristics analysis, the cut-off values for LMR and tumor length diameter were 4.85 and 28.0 mm, respectively, for parathyroid cancer prediction. When the two extracted factors were stratified by the number of factors held, the predictive ability improved as the number of factors increased.
Conclusion
In the preoperative evaluation, a combination of tumor length diameter of more than 28 mm and LMR of less than 4.85 was considered to have a high probability of cancer.
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Department of Obstetrics and Gynecology, University of Oulu and Oulu University Hospital, Medical Research Center, PEDEGO Research Unit, Oulu, Finland
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Objective
To study the use of hormone therapy (HT), morbidity and reproductive outcomes of women with primary ovarian insufficiency (POI) due to FSH-resistant ovaries (FSHRO).
Design
A prospective follow-up study in a university-based tertiary clinic setting.
Methods
Twenty-six women with an inactivating A189V FSH receptor mutation were investigated by means of a health questionnaire and clinical examination. Twenty-two returned the health questionnaire and 14 were clinically examined. Main outcome measures in the health questionnaire were reported as HT, morbidity, medication and infertility treatment outcomes. In the clinical study, risk factors for cardiovascular disease (CVD) and metabolic syndrome (MetS) were compared to age-matched controls from a national population survey (FINRISK). Average number of controls was 326 per FSHRO subject (range 178–430). Bone mineral density and whole-body composition were analyzed with DXA. Psychological and sexual well-being was assessed with Beck Depression Inventory (BDI21), Generalized Anxiety Disorder 7 (GAD-7) and Female Sexual Function Index (FSFI) questionnaires.
Results
HT was initiated late (median 18 years of age) compared with normal puberty and the median time of use was shorter (20–22 years) than the normal fertile period. Osteopenia was detected in 9/14 of the FSHRO women despite HT. No major risk factors for CVD or diabetes were found.
Conclusions
HT of 20 years seems to be associated with a similar cardiovascular and metabolic risk factor profile as in the population control group. However, optimal bone health may require an early-onset and longer period of HT, which would better correspond to the natural fertile period.
Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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Division of Musculoskeletal Section, Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
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Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
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School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan
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Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
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Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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Objective
Previous studies have suggested that body mass index (BMI) should be considered when assessing the relationship between fatty liver (FL) and osteoporosis. The aim of this study was to investigate future fracture events in people with FL, focusing on the effect of BMI in both sexes.
Methods
This retrospective cohort study, spanning from 2011 to 2019, enrolled 941 people, including 441 women and 500 men, aged 50 years or older who underwent liver imaging (ultrasound, computed tomography, or magnetic resonance image) and dual-energy X-ray absorptiometry (for bone mineral density measurements). The study examined predictors of osteoporosis in both sexes and the effect of different ranges of BMI (18.5–24, 24–27, and ≥27 kg/m2) on the risk of future fracture events in FL patients.
Results
The average follow-up period was 5.3 years for women and 4.2 years for men. Multivariate analysis identified age and BMI as independent risk factors of osteoporosis in both sexes. Each unit increase in BMI decreased the risk of osteoporosis by ≥10%. In both women and men with FL, a BMI of 24–27 kg/m2 offered protection against future fractures, compared to those without FL and with a BMI of 18.5–24 kg/m2.
Conclusion
The protective effect of a higher BMI against future fractures in middle-aged and elderly female and male patients with FL is not uniform and diminishes beyond certain BMI ranges.
