Hypoparathyroidism in the adult: Epidemiology, diagnosis, pathophysiology, target‐organ involvement, treatment, and challenges for future research
TL;DR: This review, which focuses primarily on hypoparathyroidism in the adult, provides a comprehensive summary of the latest information on this disease.
Abstract: Recent advances in understanding the epidemiology, genetics, diagnosis, clinical presentations, skeletal involvement, and therapeutic approaches to hypoparathyroidism led to the First International Workshop on Hypoparathyroidism that was held in 2009. At this conference, a group of experts convened to discuss these issues with a view towards a future research agenda for this disease. This review, which focuses primarily on hypoparathyroidism in the adult, provides a comprehensive summary of the latest information on this disease.
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TL;DR: It is suggested that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units, outpatients, and referrals to social services, but for house doctors to assess overdoses would provide no economy for the psychiatric or social services.
Abstract: admission. This proportion could already be greater in some parts of the country and may increase if referrals of cases of self-poisoning increase faster than the facilities for their assessment and management. The provision of social work and psychiatric expertise in casualty departments may be one means of preventing unnecessary medical admissions without risk to the patients. Dr Blake's and Dr Bramble's figures do not demonstrate, however, that any advantage would attach to medical teams taking over assessment from psychiatrists except that, by implication, assessments would be completed sooner by staff working on the ward full time. What the figures actually suggest is that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units (by 19°U), outpatients (by 5O°'), and referrals to social services (by 140o). So for house doctors to assess overdoses would provide no economy for the psychiatric or social services. The study does not tell us what the consequences would have been for the six patients who the psychiatrists would have admitted but to whom the house doctors would have offered outpatient appointments. E J SALTER
4,497 citations
TL;DR: Currently available data are summarized to give an overview of the effects of vitamin D on the immune system in general and on the regulation of inflammatory responses, as well as regulatory mechanisms connected to autoimmune diseases particularly in type 1 diabetes mellitus.
Abstract: Vitamin D metabolizing enzymes and vitamin D receptors are present in many cell types including various immune cells such as antigen-presenting-cells, T cells, B cells and monocytes. In vitro data show that, in addition to modulating innate immune cells, vitamin D also promotes a more tolerogenic immunological status. In vivo data from animals and from human vitamin D supplementation studies have shown beneficial effects of vitamin D on immune function, in particular in the context of autoimmunity. In this review, currently available data are summarized to give an overview of the effects of vitamin D on the immune system in general and on the regulation of inflammatory responses, as well as regulatory mechanisms connected to autoimmune diseases particularly in type 1 diabetes mellitus.
733 citations
TL;DR: This guideline is mainly based on how patients are managed in clinical practice, as reported in small case series and based on the experiences of the authors, which means it is not possible to formulate recommendations based on strict evidence.
Abstract: Hypoparathyroidism (HypoPT) is a rare (orphan) endocrine disease with low calcium and inappropriately low (insufficient) circulating parathyroid hormone levels, most often in adults secondary to thyroid surgery. Standard treatment is activated vitamin D analogues and calcium supplementation and not replacement of the lacking hormone, as in other hormonal deficiency states. The purpose of this guideline is to provide clinicians with guidance on the treatment and monitoring of chronic HypoPT in adults who do not have end-stage renal disease. We intend to draft a practical guideline, focusing on operationalized recommendations deemed to be useful in the daily management of patients. This guideline was developed and solely sponsored by The European Society of Endocrinology, supported by CBO (Dutch Institute for Health Care Improvement) and based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) principles as a methodological base. The clinical question on which the systematic literature search was based and for which available evidence was synthesized was: what is the best treatment for adult patients with chronic HypoPT? This systematic search found 1100 articles, which was reduced to 312 based on title and abstract. The working group assessed these for eligibility in more detail, and 32 full-text articles were assessed. For the final recommendations, other literature was also taken into account. Little evidence is available on how best to treat HypoPT. Data on quality of life and the risk of complications have just started to emerge, and clinical trials on how to optimize therapy are essentially non-existent. Most studies are of limited sample size, hampering firm conclusions. No studies are available relating target calcium levels with clinically relevant endpoints. Hence it is not possible to formulate recommendations based on strict evidence. This guideline is therefore mainly based on how patients are managed in clinical practice, as reported in small case series and based on the experiences of the authors.
314 citations
TL;DR: The course of disease in a large cohort of hypoparathyroid patients identified via a clinical patient data registry was characterized, finding that chronic kidney disease stage 3 or higher were 2- to 17-fold greater than age-appropriate norms.
Abstract: Context: Despite tremendous interest in hypoparathyroidism, large cohort studies describing typical treatment patterns, laboratory parameters, and rates of complications are lacking. Objective: Our objective was to characterize the course of disease in a large cohort of hypoparathyroid patients. Design and Setting: We conducted a chart review of patients with permanent hypoparathyroidism identified via a clinical patient data registry. Patients were seen at a Boston tertiary-care hospital system between 1988 and 2009. Patients: We identified 120 patients. Diagnosis was confirmed by documented hypocalcemia with a simultaneous low or inappropriately normal PTH level for at least 1 yr. Mean age at the end of the observation period was 52 ± 19 (range 2–87) yr, and the cohort was 73% female. Main Outcome Measure: We evaluated serum and urine laboratory results and renal and brain imaging. Results: We calculated time-weighted average serum calcium measurements for all patients. The time-weighted average for cal...
286 citations
Cites background from "Hypoparathyroidism in the adult: Ep..."
...For patients with hypoparathyroidism, experts recommend a goal serum calcium in the low-normal range and acalcium-phosphateproductof less than55mg(2)/dl(2) (1, 2)....
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...00) Teriparatide ( g/d) 2 (2) Patient 74, 40 g 5 d/wk, 60 g 2 d/wk; patient 101, 20 g daily Thiazide 24 (20) Hydrochlorothiazide (mg/d) 23 (19) 31 15 (mode, 25; range, 12....
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...Hypoparathyroidism is a rare disorder characterized by low or inappropriately normal levels of PTH in the setting of hypocalcemia (1, 2)....
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...Of the most recent measurements, 14 (26% of measured) were hypercalciuric with urinary calcium over 300 mg (1, 2)....
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TL;DR: Effective management of mild to moderate potential or actual postoperative hypoPT can be achieved by administering either empiric/prophylactic oral calcium and vitamin D, selective oral calcium, and Vitamin D based on rapid postoperative PTH level(s), or serial serum calcium levels as a guide.
Abstract: Background: Hypoparathyroidism (hypoPT) is the most common complication following bilateral thyroid operations. Thyroid surgeons must employ strategies for minimizing and preventing post-thyroidect...
237 citations
References
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TL;DR: The role of vitamin D in skeletal and nonskeletal health is considered and strategies for the prevention and treatment ofitamin D deficiency are suggested.
Abstract: Once foods in the United States were fortified with vitamin D, rickets appeared to have been conquered, and many considered major health problems from vitamin D deficiency resolved. But vitamin D deficiency is common. This review considers the role of vitamin D in skeletal and nonskeletal health and suggests strategies for the prevention and treatment of vitamin D deficiency.
11,849 citations
TL;DR: It is suggested that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units, outpatients, and referrals to social services, but for house doctors to assess overdoses would provide no economy for the psychiatric or social services.
Abstract: admission. This proportion could already be greater in some parts of the country and may increase if referrals of cases of self-poisoning increase faster than the facilities for their assessment and management. The provision of social work and psychiatric expertise in casualty departments may be one means of preventing unnecessary medical admissions without risk to the patients. Dr Blake's and Dr Bramble's figures do not demonstrate, however, that any advantage would attach to medical teams taking over assessment from psychiatrists except that, by implication, assessments would be completed sooner by staff working on the ward full time. What the figures actually suggest is that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units (by 19°U), outpatients (by 5O°'), and referrals to social services (by 140o). So for house doctors to assess overdoses would provide no economy for the psychiatric or social services. The study does not tell us what the consequences would have been for the six patients who the psychiatrists would have admitted but to whom the house doctors would have offered outpatient appointments. E J SALTER
4,497 citations
"Hypoparathyroidism in the adult: Ep..." refers background in this paper
...1,25(OH)2D3 (calcitriol), the active metabolite of vitamin D, maintains serum calcium, in part, by improving the efficiency of intestinal calcium absorption.((110)) It also promotes bone remodeling through the RANKL signaling pathway....
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...It also promotes bone remodeling through the RANKL signaling pathway.((108,110))...
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TL;DR: Treatment of postmenopausal osteoporosis with parathyroid hormone decreases the risk of vertebral and nonvertebral fractures; increases vertebral, femoral, and total-body bone mineral density; and is well tolerated.
Abstract: Background Once-daily injections of parathyroid hormone or its amino-terminal fragments increase bone formation and bone mass without causing hypercalcemia, but their effects on fractures are unknown. Methods We randomly assigned 1637 postmenopausal women with prior vertebral fractures to receive 20 or 40 μg of parathyroid hormone (1-34) or placebo, administered subcutaneously by the women daily. We obtained vertebral radiographs at base line and at the end of the study (median duration of observation, 21 months) and performed serial measurements of bone mass by dual-energy x-ray absorptiometry. Results New vertebral fractures occurred in 14 percent of the women in the placebo group and in 5 percent and 4 percent, respectively, of the women in the 20-μg and 40-μg parathyroid hormone groups; the respective relative risks of fracture in the 20-μg and 40-μg groups, as compared with the placebo group, were 0.35 and 0.31 (95 percent confidence intervals, 0.22 to 0.55 and 0.19 to 0.50). New nonvertebral fragili...
4,229 citations
"Hypoparathyroidism in the adult: Ep..." refers background in this paper
...Overall, these changes in trabecular and cortical skeletal compartments recall the pattern seen with PTH treatment of osteoporosis in individuals who do not have hypoparathyroidism.((147))...
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TL;DR: This report guides the use of diagnostics and management for this condition in clinical practice by establishing consensus at a group meeting and at subsequent discussions.
Abstract: Objective: Asymptomatic primary hyperparathyroidism (PHPT) is a common clinical problem. The purpose of this report is to guide the use of diagnostics and management for this condition in clinical practice. Participants: Interested professional societies selected representatives for the consensus committee and provided funding for a one-day meeting. A subgroup of this committee set the program and developed key questions for review. Consensus was established at a closed meeting that followed and at subsequent discussions. Evidence: Each question was addressed by a relevant literature search (on PubMed), and the data were presented for discussion at the group meeting. Consensus Process: Consensus was achieved by a group meeting. Statements were prepared and reviewed by all authors who represented the Planning Committee and the participating professional societies.
1,474 citations
"Hypoparathyroidism in the adult: Ep..." refers background in this paper
...(28,29) Homozygous mutations in the pre-pro-PTH gene cause very low or undetectable levels of PTH, leading to symptomatic hypocalcemia and hyperphosphatemia....
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...Finally, one looks forward to a time when the missing hormone, namely, PTH, will become the standard option for therapy of this disease....
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...Although much less common than its counterpart, primary hyperparathyroidism (PHPT), a disease characterized by overproduction of PTH,((1)) hypoparathyroidism, like PHPT, also presents many therapeutic challenges....
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...In patients who present with hypoparathyroidism and multiple anomalies beyond the parathyroid gland, the following conditions should be considered: (1) DiGeorge syndrome,((74,75)) (2) mitochondrial gene mutations,((76,77)) and (3) HRD syndrome....
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...This circulating species, termed N-PTH, represents less than 10% of the immunoreactivity detected by these third-generation assays in normal subjects and up to 15% in advanced renal failure....
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TL;DR: The clinical spectrum in patients with APECED is broad, and the majority of patients have three to five manifestations, some of which may not appear until the fifth decade, therefore, all patients need lifelong follow-up for the detection of new components of the disease.
Abstract: To define the clinical picture and course of the autosomal recessive disease called autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), we report data from our 10-month to 31-year follow-up of 68 patients from 54 families, now 10 months to 53 years of age. The clinical manifestations varied greatly and included from one to eight disease components, 63 percent of the patients having three to five of them. The initial manifestation was oral candidiasis in 41 patients (60 percent), intestinal malabsorption in 6 (9 percent), and keratopathy in 2 (3 percent). All the patients had candidiasis at some time. The earliest endocrine component appeared at 19 months to 35 years of age. Hypoparathyroidism was present in 54 patients (79 percent), adrenocortical failure in 49 (72 percent), and gonadal failure in 15 (60 percent) of the female patients greater than or equal to 13 years of age and 4 (14 percent) of the male patients greater than or equal to 16 years of age. There were multiple endocrine deficiencies in half the patients. From 4 to 29 percent of the patients had periodic malabsorption, gastric parietal-cell atrophy, hepatitis, alopecia, vitiligo, or a combination of these conditions. Dental-enamel hypoplasia and keratopathy were also frequent but were not attributable to hypoparathyroidism. In the patients whose initial manifestation (other than candidiasis) was adrenal failure, the other components developed less often than in the remaining patients. We conclude that the clinical spectrum in patients with APECED is broad. The majority of patients have three to five manifestations, some of which may not appear until the fifth decade. Therefore, all patients need lifelong follow-up for the detection of new components of the disease.
944 citations
"Hypoparathyroidism in the adult: Ep..." refers background in this paper
...Hypoparathyroidism is a prominent component of APS-1, also known as autoimmune polyendocrinopathy-candidiasisectodermal dystrophy (APECED).((48)) Polyglandular autoimmune syndrome type 1 is also abbreviated as PGA-1 and PAS-1....
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