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Open access

Sofya Gronskaia, Galina Melnichenko, Liudmila Rozhinskaya, Tatiana Grebennikova, Elizaveta Mamedova, Ekaterina Pigarova, Elena Przhialkovskaya, Larisa Dzeranova, Ivan Dedov, Valentin Fadeyev, Maria Luisa Brandi, and Zhanna Belaya

Hypoparathyroidism and pseudohypoparathyroidism are rare endocrine disorders, characterized by low serum calcium due to inappropriate parathyroid hormone (PTH) levels or resistance to its action. There is little epidemiological information regarding chronic hypoparathyroidism in Russia. This study aims to build a registry database of Russian patients with chronic hypoparathyroidism who were referred for hospital treatment in order to conduct initial analysis of clinical presentations and hospital management. The Italian registry model was taken to be able to integrate our data in the future. Two hundred patients with hypoparathyroidism (n = 194) and pseudohypoparathyroidism (n = 6) were enrolled over 2 years (2017–2019). The most frequent cause of hypoparathyroidism was neck surgery (82.5%, mostly females), followed by idiopathic hypoparathyroidism (10%), syndromic forms of genetic hypoparathyroidism (4.5%) and forms of defective PTH action (3%). Calcium supplements and alfacalcidol were prescribed in most cases. However, a minority of patients (n = 6) needed to receive teriparatide as the only way to maintain calcium levels and to prevent symptoms of hypocalcemia. Consequently, substitution treatment with parathyroid hormone should be available in certain cases of hypoparathyroidism. This database will be useful to estimate the potential requirement for recombinant PTH in Russia and standards for clinical and therapeutic approaches.

Open access

Cristina Lamas, Elena Navarro, Anna Casterás, Paloma Portillo, Victoria Alcázar, María Calatayud, Cristina Álvarez-Escolá, Julia Sastre, Evangelina Boix, Lluis Forga, Almudena Vicente, Josep Oriola, Jordi Mesa, and Nuria Valdés

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.

Open access

Anna Gorbacheva, Anna Eremkina, Daria Goliusova, Julia Krupinova, and Natalia Mokrysheva

Multiple endocrine neoplasia type 1 (MEN1) is the most common cause of hereditary primary hyperparathyroidism (PHPT). Bone disorders are considered one of the key symptoms in PHPT present with the significant reduction in bone mineral density and low-energy fractures. Previously, these bone disorders were believed to be caused solely by the increase in the level of parathyroid hormone and its subsequent effect on bone resorption. The current paradigm, however, states that the mutations in the menin gene, which cause the development of MEN1, can also affect the metabolism of the cells of the osteoid lineage. This review analyzes both the proven and the potential intracellular mechanisms through which menin can affect bone metabolism.

Open access

Emmanuelle Noirrit, Mélissa Buscato, Marion Dupuis, Bernard Payrastre, Coralie Fontaine, Jean-François Arnal, and Marie-Cécile Valera

Estrogen–progestin therapy was previously considered as the standard of care for managing bothersome symptoms associated with menopause, but it increases risks of breast cancer and of thromboembolism. The combination of conjugated estrogen (CE) with bazedoxifene (BZA) named tissue-selective estrogen complex (TSEC) was designed to minimize or even abrogate the undesirable effects on breast, while maintaining the beneficial effects such as prevention of osteoporosis and suppression of climacteric symptoms. The risk on thromboembolism associated with TSEC is unknown, although the clinical available data are reassuring. The aim of this study was to define the impact of a chronic administration of CE, BZA or CE + BZA on hemostasis and thrombosis in ovariectomized mice. As expected, CE, but not BZA neither CE + BZA, induced uterine and vagina hypertrophy. As previously demonstrated for 17β-estradiol (E2), we found that CE (i) increased tail-bleeding time, (ii) prevented occlusive thrombus formation in injured carotid artery and (iii) protected against collagen/epinephrine-induced thromboembolism. Thus, whereas BZA antagonized CE action on reproductive tissues, it had no impact on the effect of CE on hemostasis, thromboembolism and arterial thrombosis in mice. CE + BZA shared the anti-thrombotic actions of CE in these mouse models. If a similar process is at work in women, CE combined with BZA could contribute to minimize the risk of thrombosis associated with hormone replacement therapy.

Open access

Panagiotis Anagnostis, Irene Lambrinoudaki, John C Stevenson, and Dimitrios G Goulis

Cardiovascular disease (CVD) is of major concern in women entering menopause. The changing hormonal milieu predisposes them to increased CVD risk, due to a constellation of risk factors, such as visceral obesity, atherogenic dyslipidemia, dysregulation in glucose homeostasis, non-alcoholic fatty liver disease and arterial hypertension. However, an independent association of menopause per se with increased risk of CVD events has only been proven for early menopause (<45 years). Menopausal hormone therapy (MHT) ameliorates most of the CVD risk factors mentioned above. Transdermal estrogens are the preferable regimen, since they do not increase triglyceride concentrations and they are not associated with increased risk of venous thromboembolic events (VTE). Although administration of MHT should be considered on an individual basis, MHT may reduce CVD morbidity and mortality, if commenced during the early postmenopausal period (<60 years or within ten years since the last menstrual period). In women with premature ovarian insufficiency (POI), MHT should be administered at least until the average age of menopause (50–52 years). MHT is contraindicated in women with a history of VTE and is not currently recommended for the sole purpose of CVD prevention. The risk of breast cancer associated with MHT is generally low and is mainly conferred by the progestogen. Micronized progesterone and dydrogesterone are associated with lower risk compared to other progestogens.

Open access

Katherine U Gaynor, Irina V Grigorieva, Samantha M Mirczuk, Sian E Piret, Kreepa G Kooblall, Mark Stevenson, Karine Rizzoti, Michael R Bowl, M Andrew Nesbit, Paul T Christie, William D Fraser, Tertius Hough, Michael P Whyte, Robin Lovell-Badge, and Rajesh V Thakker

Hypoparathyroidism is genetically heterogeneous and characterized by low plasma calcium and parathyroid hormone (PTH) concentrations. X-linked hypoparathyroidism (XLHPT) in two American families is associated with interstitial deletion-insertions involving deletions of chromosome Xq27.1 downstream of SOX3 and insertions of predominantly non-coding DNA from chromosome 2p25.3. These could result in loss, gain, or movement of regulatory elements, which include ultraconserved element uc482, which could alter SOX3 expression. To investigate this, we analysed SOX3 expression in EBV-transformed lymphoblastoid cells from three affected males, three unaffected males, and four carrier females from one XLHPT family. SOX3 expression was similar in all individuals, indicating that the spatiotemporal effect of the interstitial deletion-insertion on SOX3 expression postulated to occur in developing parathyroids did not manifest in lymphoblastoids. Expression of SNTG2, which is duplicated and inserted into the X chromosome, and ATP11C, which is moved telomerically, were also similarly expressed in all individuals. Investigation of male hemizygous (Sox3−/Y and uc482−/Y) and female heterozygous (Sox3+/ and uc482+/) knockout mice, together with wild-type littermates (male Sox3+/Y and uc482+/Y, and female Sox3+/+ and uc482+/+), revealed Sox3−/Y, Sox3+/, uc482/Y, and uc482+/ mice to have normal plasma biochemistry, compared to their respective wild-type littermates. When challenged with a low calcium diet, all mice had hypocalcaemia, and elevated plasma PTH concentrations and alkaline phosphatase activities, and Sox3−/Y, Sox3+/, uc482−/Y, and uc482+/ mice had similar plasma biochemistry, compared to wild-type littermates. Thus, these results indicate that absence of Sox3 or uc482 does not cause hypoparathyroidism and that XLHPT likely reflects a more complex mechanism.

Open access

Clarissa Souza Barthem, Camila Lüdke Rossetti, Denise P Carvalho, and Wagner Seixas da-Silva

Estradiol has been used to prevent metabolic diseases, bone loss and menopausal symptoms, even though it might raise the risk of cancer. Metformin is usually prescribed for type 2 diabetes mellitus and lowers food intake and body mass while improving insulin resistance and the lipid profile. Ovariectomized rats show increased body mass, insulin resistance and changes in the lipid profile. Thus, the aim of this work was to evaluate whether metformin could prevent the early metabolic dysfunction that occurs early after ovariectomy. Female Wistar rats were divided into the following groups: SHAM-operated (SHAM), ovariectomized (OVX), ovariectomized + estradiol (OVX + E2) and ovariectomized + metformin (OVX + M). Treatment with metformin diminished approximately 50% of the mass gain observed in ovariectomized animals and reduced both the serum and hepatic triglyceride levels. The hepatic levels of phosphorylated AMP-activated protein kinase (pAMPK) decreased after OVX, and the expression of the inactive form of hepatic acetyl-CoA carboxylase (ACC) was also reduced. Metformin was able to increase the levels of pAMPK in the liver of OVX animals, sustaining the balance between the inactive and total forms of ACC. Estradiol effects were similar to those of metformin but with different proportions. Our results suggest that metformin ameliorates the early alterations of metabolic parameters and rescues hepatic AMPK phosphorylation and ACC inactivation observed in ovariectomized rats.

Open access

Marília D’Elboux Guimarães Brescia, Karine Candido Rodrigues, André Fernandes d’Alessandro, Wellington Alves Filho, Willemijn Y van der Plas, Schelto Kruijff, Sergio Samir Arap, Sergio Pereira de Almeida Toledo, Fábio Luiz de Menezes Montenegro, and Delmar Muniz Lourenço Jr

Background

Potential influences of parathyroidectomy (PTx) on the quality of life (QoL) in multiple endocrine neoplasia type 1-related primary hyperparathyroidism (HPT/MEN1) are unknown.

Method

Short Form 36 Health Survey Questionnaire was prospectively applied to 30 HPT/MEN1 patients submitted to PTx (20, subtotal; 10, total with autograft) before, 6 and 12 months after surgery. Parameters that were analyzed included QoL, age, HPT-related symptoms, general pain, comorbidities, biochemical/hormonal response, PTx type and parathyroid volume.

Results

Asymptomatic patients were younger (30 vs 38 years; P = 0.04) and presented higher QoL scores than symptomatic ones: Physical Component Summary score (PCS) 92.5 vs 61.2, P = 0.0051; Mental Component Summary score (MCS) 82.0 vs 56.0, P = 0.04. In both groups, QoL remained stable 1 year after PTx, independently of the number of comorbidities. Preoperative general pain was negatively correlated with PCS (r = −0.60, P = 0.0004) and MCS (r = −0.57, P = 0.0009). Also, moderate/intense pain was progressively (6/12 months) more frequent in cases developing hypoparathyroidism. The PTx type and hypoparathyroidism did not affect the QoL at 12 months although remnant parathyroid tissue volume did have a positive correlation (P = 0.0490; r = 0.3625) to PCS 12 months after surgery. Patients with one to two comorbidities had as pre-PTx PCS (P = 0.0015) as 12 months and post-PTx PCS (P = 0.0031) and MCS (P = 0.0365) better than patients with three to four comorbidities.

Conclusion

A variable QoL profile was underscored in HPT/MEN1 reflecting multiple factors associated with this complex disorder as comorbidities, advanced age at PTx and presence of preoperative symptoms or of general pain perception. Our data encourage the early indication of PTx in HPT/MEN1 by providing known metabolic benefits to target organs and avoiding potential negative impact on QoL.

Open access

Kaiyu Pan, Chengyue Zhang, Xiaocong Yao, and Zhongxin Zhu

Aim

Ensuring adequate calcium (Ca) intake during childhood and adolescence is critical to acquire good peak bone mass to prevent osteoporosis during older age. As one of the primary strategies to build and maintain healthy bones, we aimed to determine whether dietary Ca intake has an influence on bone mineral density (BMD) in children and adolescents.

Methods

We conducted a cross-sectional study composed of 10,092 individuals from the National Health and Nutrition Examination Survey (NHANES). Dietary Ca intake and total BMD were taken as independent and dependent variables, respectively. To evaluate the association between them, we conducted weighted multivariate linear regression models and smooth curve fittings.

Results

There was a significantly positive association between dietary Ca intake and total BMD. The strongest association was observed in 12–15 year old whites, 8–11 year old and 16–19 year old Mexican Americans, and 16–19 year old individuals from other race/ethnicity, in whom each quintile of Ca intake was increased. We also found that there were significant inflection points in females, blacks, and 12–15 year old adolescents group, which means that their total BMD would decrease when the dietary Ca intake was more than 2.6–2.8 g/d.

Conclusions

This cross-sectional study indicated that a considerable proportion of children and adolescents aged 8–19 years would attain greater total BMD if they increased their dietary Ca intake. However, higher dietary Ca intake (more than 2.6–2.8 g/d) is associated with lower total BMD in females, blacks, and 12–15 year old adolescents group.

Open access

Henryk F Urbanski, Kevin Mueller, and Cynthia L Bethea

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.