Search Results

You are looking at 1 - 10 of 75 items for :

  • Abstract: Hypoparathyroidism x
  • Abstract: Osteo* x
Clear All Modify Search
Sofya Gronskaia Endocrinology Research Centre, Moscow, Russia

Search for other papers by Sofya Gronskaia in
Google Scholar
PubMed
Close
,
Galina Melnichenko Endocrinology Research Centre, Moscow, Russia

Search for other papers by Galina Melnichenko in
Google Scholar
PubMed
Close
,
Liudmila Rozhinskaya Endocrinology Research Centre, Moscow, Russia

Search for other papers by Liudmila Rozhinskaya in
Google Scholar
PubMed
Close
,
Tatiana Grebennikova Endocrinology Research Centre, Moscow, Russia

Search for other papers by Tatiana Grebennikova in
Google Scholar
PubMed
Close
,
Elizaveta Mamedova Endocrinology Research Centre, Moscow, Russia

Search for other papers by Elizaveta Mamedova in
Google Scholar
PubMed
Close
,
Ekaterina Pigarova Endocrinology Research Centre, Moscow, Russia

Search for other papers by Ekaterina Pigarova in
Google Scholar
PubMed
Close
,
Elena Przhialkovskaya Endocrinology Research Centre, Moscow, Russia

Search for other papers by Elena Przhialkovskaya in
Google Scholar
PubMed
Close
,
Larisa Dzeranova Endocrinology Research Centre, Moscow, Russia

Search for other papers by Larisa Dzeranova in
Google Scholar
PubMed
Close
,
Ivan Dedov Endocrinology Research Centre, Moscow, Russia

Search for other papers by Ivan Dedov in
Google Scholar
PubMed
Close
,
Valentin Fadeyev I.M. Sechenov First Moscow State Medical University, Moscow, Russia

Search for other papers by Valentin Fadeyev in
Google Scholar
PubMed
Close
,
Maria Luisa Brandi University of Florence, Surgery and Translational Medicine, Piereccaini, Firenze, Italy

Search for other papers by Maria Luisa Brandi in
Google Scholar
PubMed
Close
, and
Zhanna Belaya Endocrinology Research Centre, Moscow, Russia

Search for other papers by Zhanna Belaya in
Google Scholar
PubMed
Close

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
Leyre Lorente-Poch Endocrine Surgery Unit, Hospital del Mar, Barcelona, Spain
Departament de Cirurgia, Universitat Autònoma de Barcelona, Barcelona, Spain

Search for other papers by Leyre Lorente-Poch in
Google Scholar
PubMed
Close
,
Sílvia Rifà-Terricabras Departament de Cirurgia, Universitat Autònoma de Barcelona, Barcelona, Spain

Search for other papers by Sílvia Rifà-Terricabras in
Google Scholar
PubMed
Close
,
Juan José Sancho Endocrine Surgery Unit, Hospital del Mar, Barcelona, Spain
Departament de Cirurgia, Universitat Autònoma de Barcelona, Barcelona, Spain

Search for other papers by Juan José Sancho in
Google Scholar
PubMed
Close
,
Danilo Torselli-Valladares Endocrine Surgery Unit, Hospital del Mar, Barcelona, Spain

Search for other papers by Danilo Torselli-Valladares in
Google Scholar
PubMed
Close
,
Sofia González-Ortiz Department of Radiology, Hospital del Mar, Barcelona, Spain

Search for other papers by Sofia González-Ortiz in
Google Scholar
PubMed
Close
, and
Antonio Sitges-Serra Endocrine Surgery Unit, Hospital del Mar, Barcelona, Spain
Departament de Cirurgia, Universitat Autònoma de Barcelona, Barcelona, Spain

Search for other papers by Antonio Sitges-Serra in
Google Scholar
PubMed
Close

Objective:

Permanent hypoparathyroidism is an uncommon disease resulting most frequently from neck surgery. It has been associated with visceral calcifications but few studies have specifically this in patients with post-surgical hypoparathyroidism. The aim of the present study was to assess the prevalence of basal ganglia and carotid artery calcifications in patients with long-term post-thyroidectomy hypoparathyroidism compared with a control population.

Design:

Case–control study.

Methods:

A cross-sectional review comparing 29 consecutive patients with permanent postoperative hypoparathyroidism followed-up in a tertiary reference unit for Endocrine Surgery with a contemporary control group of 501 patients who had an emergency brain CT scan. Clinical variables and prevalence of basal ganglia and carotid artery calcifications were recorded.

Results:

From a cohort of 46 patients diagnosed with permanent hypoparathyroidism, 29 were included in the study. The mean duration of disease was 9.2 ± 7 years. Age, diabetes, hypertension, smoking and dyslipidemia were similarly distributed in case and control groups. The prevalence of carotid artery and basal ganglia calcifications was 4 and 20 times more frequent in patients with permanent hypoparathyroidism, respectively. After propensity score matching of the 28 the female patients, 68 controls were matched for age and presence of cardiovascular factors. Cases showed a four-fold prevalence of basal ganglia calcifications, whereas that of carotid calcifications was similar between cases and controls.

Conclusion:

A high prevalence of basal ganglia calcifications was observed in patients with post-surgical permanent hypoparathyroidism. It remains unclear whether carotid artery calcification may also be increased.

Open access
Rasmus Reinke Department of Otorhinolaryngology, Head and Neck Surgery, Aarhus University Hospital, Aarhus, Denmark

Search for other papers by Rasmus Reinke in
Google Scholar
PubMed
Close
,
Stefano Christian Londero Department of Otorhinolaryngology, Head and Neck Surgery, Aarhus University Hospital, Aarhus, Denmark

Search for other papers by Stefano Christian Londero in
Google Scholar
PubMed
Close
,
Martin Almquist Department of Surgery, Lund University Hospital, Lund, Sweden

Search for other papers by Martin Almquist in
Google Scholar
PubMed
Close
,
Lars Rejnmark Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

Search for other papers by Lars Rejnmark in
Google Scholar
PubMed
Close
, and
Lars Rolighed Department of Otorhinolaryngology, Head and Neck Surgery, Aarhus University Hospital, Aarhus, Denmark

Search for other papers by Lars Rolighed in
Google Scholar
PubMed
Close

Objective

Total thyroidectomy is associated with a high risk of postoperative hypoparathyroidism, mainly due to the unintended surgical damage to the parathyroid glands or their blood supply. It is possible that surgeons who also perform parathyroid surgery see lower rates of postoperative hypoparathyroidism. In a single institution, we investigated the effects of restricting total thyroidectomy operations for Graves’ disease to two surgeons who performed both thyroid and parathyroid surgeries. We aimed to evaluate the rates of postoperative hypoparathyroidism in a 10-year period with primary attention toward patients with Graves’ disease.

Design

Retrospective cohort study from a single institution.

Methods

We defined the rate of permanent hypoparathyroidism after total thyroidectomy as the need for active vitamin D 6 months postoperatively. Between 2012 and 2016, seven surgeons performed all thyroidectomies. From January 2017, only surgeons also performing parathyroid surgery carried out thyroidectomies for Graves’ disease.

Results

We performed total thyroidectomy in 543 patients. The rate of permanent hypoparathyroidism decreased from 28% in 2012–2014 to 6% in 2020–2021. For patients with Graves’ disease, the rate of permanent hypoparathyroidism decreased from 36% (13 out of 36) in 2015–2016 to 2% (1 out of 56) in 2020–2021. In cancer patients, the rate of permanent hypoparathyroidism decreased from 30% (14 out of 46) in 2012–2014 to 10% (10 out of 51) in 2020–2021.

Conclusion

Restricting thyroidectomy to surgeons who also performed parathyroid operations reduced postoperative hypoparathyroidism markedly. Accordingly, we recommend centralisation of the most difficult thyroid operations to centres and surgeons with extensive experience in parathyroid surgery.

Significance statement

Thyroid surgery is performed by many different surgeons with marked differences in outcome. Indeed, the risk of postoperative permanent hypoparathyroidism may be very high in low-volume centres. This serious condition affects the quality of life and increases long-term morbidity and the patients develop a life-long dependency of medical treatments. We encountered a high risk of hypoparathyroidism after the operation for Graves’ disease and restricted the number of surgeons to two for these operations. Further, these surgeons were experienced in both thyroid and parathyroid surgeries. We show a dramatic reduction in postoperative hypoparathyroidism after this change. Accordingly, we recommend centralisation of total thyroidectomy to surgeons with experience in both thyroid and parathyroid procedures.

Open access
Anping Su Department of Thyroid Surgery, West China Hospital, Sichuan University, Chengdu, China

Search for other papers by Anping Su in
Google Scholar
PubMed
Close
,
Yanping Gong Department of Thyroid Surgery, West China Hospital, Sichuan University, Chengdu, China

Search for other papers by Yanping Gong in
Google Scholar
PubMed
Close
,
Wenshuang Wu Department of Thyroid Surgery, West China Hospital, Sichuan University, Chengdu, China

Search for other papers by Wenshuang Wu in
Google Scholar
PubMed
Close
,
Rixiang Gong Department of Thyroid Surgery, West China Hospital, Sichuan University, Chengdu, China

Search for other papers by Rixiang Gong in
Google Scholar
PubMed
Close
,
Zhihui Li Department of Thyroid Surgery, West China Hospital, Sichuan University, Chengdu, China

Search for other papers by Zhihui Li in
Google Scholar
PubMed
Close
, and
Jingqiang Zhu
Search for other papers by Jingqiang Zhu in
Google Scholar
PubMed
Close

Background

The effect of parathyroid autotransplantation on hypoparathyroidism is not fully understood. The purpose of the study was to determine the effect of autotransplantation of a parathyroid gland on the incidence of hypoparathyroidism and recovery of parathyroid function at 6 months after total thyroidectomy with central neck dissection for papillary thyroid carcinoma.

Methods

All patients with autotransplantation of a parathyroid gland (no inadvertent parathyroidectomy) (group A), in situ preservation of all parathyroid glands (no autotransplantation and inadvertent parathyroidectomy) (group B) or inadvertent removal of a parathyroid gland (no autotransplantation) (group C) who underwent first-time total thyroidectomy with central neck dissection for papillary thyroid carcinoma between January 2013 and June 2016 were included retrospectively.

Results

Of the 702 patients, 383, 297 and 22 were respectively included in the groups A, B and C. The overall rates of transient and permanent hypoparathyroidism were 37.6% and 1.0%. The incidence of transient hypoparathyroidism was 43.9, 29.0 and 45.5% (A vs B, P = 0.000; A vs C, P = 1.000), and the incidence of permanent hypoparathyroidism was 1.0, 0.7 and 4.5% (P > 0.05). The recovery rates of serum parathyroid hormone levels were 71.4, 72.2 and 66.0% at 6-month follow-up (P > 0.05).

Conclusion

Autotransplantation of a parathyroid gland does not affect the incidence of permanent hypoparathyroidism, but increases the risk of transient hypoparathyroidism when the rest of parathyroid glands are preserved in situ. At least 2 parathyroid glands should be preserved during total thyroidectomy with central neck dissection to prevent permanent hypoparathyroidism.

Open access
A Chinoy Royal Manchester Children’s Hospital, Manchester, UK

Search for other papers by A Chinoy in
Google Scholar
PubMed
Close
,
M Skae Royal Manchester Children’s Hospital, Manchester, UK

Search for other papers by M Skae in
Google Scholar
PubMed
Close
,
A Babiker King Abdullah Specialized Children’s Hospital, Riyadh, Saudi Arabia

Search for other papers by A Babiker in
Google Scholar
PubMed
Close
,
D Kendall Royal Preston Hospital, Preston, UK

Search for other papers by D Kendall in
Google Scholar
PubMed
Close
,
M Z Mughal Royal Manchester Children’s Hospital, Manchester, UK

Search for other papers by M Z Mughal in
Google Scholar
PubMed
Close
, and
R Padidela Royal Manchester Children’s Hospital, Manchester, UK

Search for other papers by R Padidela in
Google Scholar
PubMed
Close

Background

Hypoparathyroidism is characterised by hypocalcaemia, and standard management is with an active vitamin D analogue and adequate oral calcium intake (dietary and/or supplements). Little is described in the literature about the impact of intercurrent illnesses on calcium homeostasis in children with hypoparathyroidism.

Methods

We describe three children with hypoparathyroidism in whom intercurrent illnesses led to hypocalcaemia and escalation of treatment with alfacalcidol (1-hydroxycholecalciferol) and calcium supplements.

Results

Three infants managed with standard treatment for hypoparathyroidism (two with homozygous mutations in GCMB2 gene and one with Sanjad-Sakati syndrome) developed symptomatic hypocalcaemia (two infants developed seizures) following respiratory or gastrointestinal illnesses. Substantial increases in alfacalcidol doses (up to three times their pre-illness doses) and calcium supplementation were required to achieve acceptable serum calcium concentrations. However, following resolution of illness, these children developed an increase in serum calcium and hypercalciuria, necessitating rapid reduction to pre-illness dosages of alfacalcidol and oral calcium supplementation.

Conclusion

Intercurrent illness may precipitate symptomatic hypocalcaemia in children with hypoparathyroidism, necessitating increase in dosages of alfacalcidol and calcium supplements. Close monitoring is required on resolution of the intercurrent illness, with timely reduction of dosages of active analogues of vitamin D and calcium supplements to prevent hypercalcaemia, hypercalciuria and nephrocalcinosis.

Open access
Guido Zavatta Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy

Search for other papers by Guido Zavatta in
Google Scholar
PubMed
Close
and
Bart L Clarke Mayo Clinic, Rochester, Minnesota, USA

Search for other papers by Bart L Clarke in
Google Scholar
PubMed
Close

The first adjunctive hormone therapy for chronic hypoparathyroidism, recombinant human parathyroid hormone (1–84) (rhPTH(1–84)) was approved by the FDA in January 2015. Since the approval of rhPTH(1–84), growing interest has developed in other agents to treat this disorder in both the scientific community and among pharmaceutical companies. For several reasons, conventional therapy with calcium and activated vitamin D supplementation, magnesium supplementation as needed, and occasionally thiazide-type diuretic therapy remains the mainstay of treatment, while endocrinologists and patients are constantly challenged by limitations of conventional treatment. Serum calcium fluctuations, increased urinary calcium, hyperphosphatemia, and a constellation of symptoms that limit mental and physical functioning are frequently associated with conventional therapy. Understanding how conventional treatment and hormone therapy work in terms of pharmacokinetics and pharmacodynamics is key to effectively managing chronic hypoparathyroidism. Multiple questions remain regarding the effectiveness of PTH adjunctive therapy in preventing or slowing the onset and progression of the classical complications of hypoparathyroidism, such as chronic kidney disease, calcium-containing kidney stones, cataracts, or basal ganglia calcification. Several studies point toward an improvement in the quality of life during replacement therapy. This review will discuss current clinical and research challenges posed by treatment of chronic hypoparathyroidism.

Key points:

  • Conventional therapy with calcium and activated forms of vitamin D are currently the mainstays of treatment for most patients with chronic hypoparathyroidism.

  • Hormone therapy can be administered through FDA-approved once-daily rhPTH(1–84), or off-label multiple-daily injections of teriparatide. The former is the only FDA-approved drug, with safety and efficacy supported by a randomized placebo-controlled trial and open-label long-term extension trial data.

  • Twice-daily teriparatide has been used in children safely for up to 10 years.

  • New pharmacological options that replace the deficient hormone wi ll likely be available within the next few years.

Open access
Jean-Philippe Bertocchio Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Physiologie, Paris, France
Centre de Référence des Maladies Rares du Calcium et du Phosphore Filière de Santé Maladies Rares OSCAR, Paris, France
Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, INSERM, UMRS1138, Paris, France

Search for other papers by Jean-Philippe Bertocchio in
Google Scholar
PubMed
Close
,
Natalie Grosset Hypoparathyroïdisme France, Annecy, France

Search for other papers by Natalie Grosset in
Google Scholar
PubMed
Close
,
Lionel Groussin Department of Endocrinology, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Université de Paris, Paris, France

Search for other papers by Lionel Groussin in
Google Scholar
PubMed
Close
,
Peter Kamenický Université Paris-Saclay, Inserm U1185, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service d’Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphate, Le Kremlin-Bicêtre, France

Search for other papers by Peter Kamenický in
Google Scholar
PubMed
Close
,
Fabrice Larceneux Université Paris-Dauphine, PSL Research University, CNRS, UMR 7088, DRM [Ermes], Paris, France

Search for other papers by Fabrice Larceneux in
Google Scholar
PubMed
Close
,
Anne Lienhardt-Roussie CHU Dupuytren, Hôpital Mère Enfant, Endocrinologie Pédiatrique, Limoges, France

Search for other papers by Anne Lienhardt-Roussie in
Google Scholar
PubMed
Close
,
Agnès Linglart Centre de Référence des Maladies Rares du Calcium et du Phosphore Filière de Santé Maladies Rares OSCAR, Paris, France
Université Paris-Saclay, Inserm U1185, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Service d’Endocrinologie et Diabète de l’Enfant, Centre de Référence des Maladies Rares du Calcium et du Phosphore et Filière de Santé Maladies Rares OSCAR, Hôpital Bicêtre Paris Saclay, Le Kremlin-Bicêtre, France

Search for other papers by Agnès Linglart in
Google Scholar
PubMed
Close
,
Gérard Maruani Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Physiologie, Paris, France
Centre de Référence des Maladies Rares du Calcium et du Phosphore Filière de Santé Maladies Rares OSCAR, Paris, France
Assistance Publique-Hôpitaux de Paris, Institut Necker-Enfants Malades, INSERM U1151 – CNRS UMR 8253, Paris, France

Search for other papers by Gérard Maruani in
Google Scholar
PubMed
Close
,
Eric Mirallie Chirurgie Cancérologique, Digestive et Endocrine, Institut des Maladies de l’Appareil Digestif, Hôtel Dieu, CHU Nantes, France
Association Francophone de Chirurgie Endocrinienne (AFCE), France

Search for other papers by Eric Mirallie in
Google Scholar
PubMed
Close
,
François Pattou Université de Lille, CHU Lille, Institut Pasteur Lille, Inserm U1190, Lille, France

Search for other papers by François Pattou in
Google Scholar
PubMed
Close
,
Riyad N H Seervai Molecular & Cellular Biology Graduate Program, Medical Scientist Training Program, Baylor College of Medicine, Houston, Texas, USA

Search for other papers by Riyad N H Seervai in
Google Scholar
PubMed
Close
,
Coralie Sido Hypoparathyroïdisme France, Annecy, France

Search for other papers by Coralie Sido in
Google Scholar
PubMed
Close
,
Caroline Silve Centre de Référence des Maladies Rares du Calcium et du Phosphore Filière de Santé Maladies Rares OSCAR, Paris, France
Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Biochimie et Génétique Moléculaires, Paris, France
INSERM, U1169, Université Paris Sud, Hôpital Bicêtre, Le Kremlin Bicêtre, France

Search for other papers by Caroline Silve in
Google Scholar
PubMed
Close
,
Aurélie Vilfaillot Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Unité de Recherche Clinique, Paris, France
INSERM, U1418, CIC-EC, Hôpital Européen Georges Pompidou, Paris, France

Search for other papers by Aurélie Vilfaillot in
Google Scholar
PubMed
Close
,
Antoine Tabarin Service Endocrinologie Diabète et Nutrition, CHU de Bordeaux, Université de Bordeaux, Pessac, France

Search for other papers by Antoine Tabarin in
Google Scholar
PubMed
Close
,
Marie-Christine Vantyghem CHU Lille, Department of Endocrinology, Diabetology and Metabolism, Inserm U1190, EGID, Lille, France

Search for other papers by Marie-Christine Vantyghem in
Google Scholar
PubMed
Close
,
Pascal Houillier Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Physiologie, Paris, France
Centre de Référence des Maladies Rares du Calcium et du Phosphore Filière de Santé Maladies Rares OSCAR, Paris, France
Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, INSERM, UMRS1138, Paris, France
CNRS, ERL8228, Paris, France

Search for other papers by Pascal Houillier in
Google Scholar
PubMed
Close
, and
the investigators of the Épi-Hypo study
Search for other papers by the investigators of the Épi-Hypo study in
Google Scholar
PubMed
Close
the investigators of the Épi-Hypo study

Context

Recent guidelines have provided recommendations for the care of patients with chronic hypoparathyroidism. Very little is known about actual physicians’ practices or their adherence to such guidelines.

Objective

To describe the physicians’ practice patterns and their compliance with international guidelines.

Design

The cohort studies included were Épi-Hypo (118 physicians and 107 patients, from September 2016 to December 2019) and ePatients (110 patients, November 2019).

Methods

Internet-based cohorts involving all settings at a nationwide level (France). Participants were (i) physicians treating patients with chronic hypoparathyroidism and patients with chronic hypoparathyroidism either participating in the (ii) Épi-Hypo study (Épi-Hypo 2019 patients), or (iii) Hypoparathyroidism France, the national representative association (ePatients).

Results

The physicians’ specialties were mainly endocrinology (61%), nephrology (28%), family medicine (2.5%), pediatrics (2.5%), rheumatology (2%), or miscellaneous (4%) and 45% were practicing in public universities. The median number of pharmaceutical drug classes prescribed was three per patient. The combination of active vitamin D and calcium salt was given to 59 and 58% of ePatients and Épi-Hypo 2019 patients, respectively. Eighty-five percent of ePatients and 87% of physicians reported monitoring plasma calcium concentrations at a steady state at least twice a year. In 32 and 26% of cases, respectively, ePatients and physicians reported being fully in accordance with international guidelines that recommend targeting symptoms, plasma calcium and phosphate values, and urine calcium excretion.

Conclusions

The care of patients with chronic hypoparathyroidism involves physicians with very different practices, so guidelines should include and target other specialists as well as endocrinologists. Full adherence to the guidelines is low in France.

Open access
Marianne C Astor Department of Clinical Science, Department of Medicine, Department of Medicine, Pediatric Department, University of Bergen, Bergen, Norway
Department of Clinical Science, Department of Medicine, Department of Medicine, Pediatric Department, University of Bergen, Bergen, Norway

Search for other papers by Marianne C Astor in
Google Scholar
PubMed
Close
,
Kristian Løvås Department of Clinical Science, Department of Medicine, Department of Medicine, Pediatric Department, University of Bergen, Bergen, Norway
Department of Clinical Science, Department of Medicine, Department of Medicine, Pediatric Department, University of Bergen, Bergen, Norway

Search for other papers by Kristian Løvås in
Google Scholar
PubMed
Close
,
Anette S B Wolff Department of Clinical Science, Department of Medicine, Department of Medicine, Pediatric Department, University of Bergen, Bergen, Norway

Search for other papers by Anette S B Wolff in
Google Scholar
PubMed
Close
,
Bjørn Nedrebø Department of Clinical Science, Department of Medicine, Department of Medicine, Pediatric Department, University of Bergen, Bergen, Norway

Search for other papers by Bjørn Nedrebø in
Google Scholar
PubMed
Close
,
Eirik Bratland Department of Clinical Science, Department of Medicine, Department of Medicine, Pediatric Department, University of Bergen, Bergen, Norway

Search for other papers by Eirik Bratland in
Google Scholar
PubMed
Close
,
Jon Steen-Johnsen Department of Clinical Science, Department of Medicine, Department of Medicine, Pediatric Department, University of Bergen, Bergen, Norway

Search for other papers by Jon Steen-Johnsen in
Google Scholar
PubMed
Close
, and
Eystein S Husebye Department of Clinical Science, Department of Medicine, Department of Medicine, Pediatric Department, University of Bergen, Bergen, Norway
Department of Clinical Science, Department of Medicine, Department of Medicine, Pediatric Department, University of Bergen, Bergen, Norway

Search for other papers by Eystein S Husebye in
Google Scholar
PubMed
Close

Primary hypomagnesemia with secondary hypocalcemia (HSH) is an autosomal recessive disorder characterized by neuromuscular symptoms in infancy due to extremely low levels of serum magnesium and moderate to severe hypocalcemia. Homozygous mutations in the magnesium transporter gene transient receptor potential cation channel member 6 (TRPM6) cause the disease. HSH can be misdiagnosed as primary hypoparathyroidism. The aim of this study was to describe the genetic, clinical and biochemical features of patients clinically diagnosed with HSH in a Norwegian cohort. Five patients in four families with clinical features of HSH were identified, including one during a national survey of hypoparathyroidism. The clinical history of the patients and their families were reviewed and gene analyses of TRPM6 performed. Four of five patients presented with generalized seizures in infancy and extremely low levels of serum magnesium accompanied by moderate hypocalcemia. Two of the patients had an older sibling who died in infancy. Four novel mutations and one large deletion in TRPM6 were identified. In one patient two linked homozygous mutations were located in exon 22 (p.F978L) and exon 23 (p.G1042V). Two families had an identical mutation in exon 25 (p.E1155X). The fourth patient had a missense mutation in exon 4 (p.H61N) combined with a large deletion in the C-terminal end of the gene. HSH is a potentially lethal condition that can be misdiagnosed as primary hypoparathyroidism. The diagnosis is easily made if serum magnesium is measured. When treated appropriately with high doses of oral magnesium supplementation, severe hypomagnesemia is uncommon and the long-term prognosis seems to be good.

Open access
Katherine U Gaynor Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK

Search for other papers by Katherine U Gaynor in
Google Scholar
PubMed
Close
,
Irina V Grigorieva Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK

Search for other papers by Irina V Grigorieva in
Google Scholar
PubMed
Close
,
Samantha M Mirczuk Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK

Search for other papers by Samantha M Mirczuk in
Google Scholar
PubMed
Close
,
Sian E Piret Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK

Search for other papers by Sian E Piret in
Google Scholar
PubMed
Close
,
Kreepa G Kooblall Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK

Search for other papers by Kreepa G Kooblall in
Google Scholar
PubMed
Close
,
Mark Stevenson Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK

Search for other papers by Mark Stevenson in
Google Scholar
PubMed
Close
,
Karine Rizzoti The Francis Crick Institute, London, UK

Search for other papers by Karine Rizzoti in
Google Scholar
PubMed
Close
,
Michael R Bowl Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK

Search for other papers by Michael R Bowl in
Google Scholar
PubMed
Close
,
M Andrew Nesbit Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK

Search for other papers by M Andrew Nesbit in
Google Scholar
PubMed
Close
,
Paul T Christie Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK

Search for other papers by Paul T Christie in
Google Scholar
PubMed
Close
,
William D Fraser Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, UK

Search for other papers by William D Fraser in
Google Scholar
PubMed
Close
,
Tertius Hough MRC Mammalian Genetics Unit, MRC Harwell Institute, Harwell Science and Innovation Campus, Oxfordshire, UK

Search for other papers by Tertius Hough in
Google Scholar
PubMed
Close
,
Michael P Whyte Washington University in St Louis School of Medicine, Center for Metabolic Bone Disease and Molecular Research, St Louis, Missouri, USA

Search for other papers by Michael P Whyte in
Google Scholar
PubMed
Close
,
Robin Lovell-Badge The Francis Crick Institute, London, UK

Search for other papers by Robin Lovell-Badge in
Google Scholar
PubMed
Close
, and
Rajesh V Thakker Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK

Search for other papers by Rajesh V Thakker in
Google Scholar
PubMed
Close

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
Cristina Lamas Department of Endocrinology and Nutrition, Complejo Hospitalario Universitario de Albacete, Albacete, Spain

Search for other papers by Cristina Lamas in
Google Scholar
PubMed
Close
,
Elena Navarro Department of Endocrinology and Nutrition, Hospital Universitario Virgen del Rocío, Sevilla, Spain

Search for other papers by Elena Navarro in
Google Scholar
PubMed
Close
,
Anna Casterás Department of Endocrinology and Nutrition, Hospital Vall d’Hebron, Barcelona, Spain

Search for other papers by Anna Casterás in
Google Scholar
PubMed
Close
,
Paloma Portillo Department of Endocrinology and Nutrition, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain

Search for other papers by Paloma Portillo in
Google Scholar
PubMed
Close
,
Victoria Alcázar Department of Endocrinology and Nutrition, Hospital Universitario Severo Ochoa, Leganés, Spain

Search for other papers by Victoria Alcázar in
Google Scholar
PubMed
Close
,
María Calatayud Department of Endocrinology and Nutrition, Hospital Univeristario Doce de Octubre, Madrid, Spain

Search for other papers by María Calatayud in
Google Scholar
PubMed
Close
,
Cristina Álvarez-Escolá Department of Endocrinology and Nutrition, Hospital Universitario La Paz, Madrid, Spain

Search for other papers by Cristina Álvarez-Escolá in
Google Scholar
PubMed
Close
,
Julia Sastre Department of Endocrinology and Nutrition, Complejo Hospitalario de Toledo, Hospital Virgen de la Salud, Toledo, Spain

Search for other papers by Julia Sastre in
Google Scholar
PubMed
Close
,
Evangelina Boix Department of Endocrinology and Nutrition, Hospital General Universitario de Elche, Elche, Spain

Search for other papers by Evangelina Boix in
Google Scholar
PubMed
Close
,
Lluis Forga Department of Endocrinology and Nutrition, Complejo Hospitalario de Navarra, Hospital de Navarra, Pamplona, Spain

Search for other papers by Lluis Forga in
Google Scholar
PubMed
Close
,
Almudena Vicente Department of Endocrinology and Nutrition, Complejo Hospitalario de Toledo, Hospital Virgen de la Salud, Toledo, Spain

Search for other papers by Almudena Vicente in
Google Scholar
PubMed
Close
,
Josep Oriola Biochemistry and Molecular Genetics Department, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain

Search for other papers by Josep Oriola in
Google Scholar
PubMed
Close
,
Jordi Mesa Department of Endocrinology and Nutrition, Hospital Vall d’Hebron, Barcelona, Spain

Search for other papers by Jordi Mesa in
Google Scholar
PubMed
Close
, and
Nuria Valdés Department of Endocrinology and Nutrition, Hospital Universitario Central de Asturias, Oviedo, Spain

Search for other papers by Nuria Valdés in
Google Scholar
PubMed
Close

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