Corticosteroid rhythms in hypoparathyroid patients.

OBJECTIVE: Previous studies indicate a possible bidirectional stimulatory relationship between parathyroid hormone (PTH) and adrenocortical hormones, but the pattern of adrenocortical secretion in hypoparathyroidism is unknown. We aimed to characterize the adrenocortical secretion in patients with postsurgical hypoparathyroidism, and whether continuous subcutaneous PTH (1-34) infusion alters secretion patterns. DESIGN: Crossover interventional study. METHODS: We recruited 10 patients with postsurgical hypoparathyroidism with very low PTH levels on stable treatment with active vitamin D and calcium. Cortisol, cortisone, and aldosterone levels were measured in microdialysate from subcutaneous tissue over 24 h, before and during continuous subcutaneous PTH (1-34) infusion. Cortisol was also assayed in serum, saliva, and urine, and aldosterone and ACTH in serum and plasma, respectively. Ten patients with primary hyperparathyroidism and 10 healthy volunteers matched for sex and age served as controls. RESULTS: Hypoparathyroid patients displayed both ultradian and circadian rhythmicity for tissue cortisol, cortisone, and aldosterone. Tissue aldosterone and cortisone levels were significantly lower in hypoparathyroid patients than in healthy controls, with no difference in tissue cortisol, but a higher cortisol to cortisone ratio. Treatment with PTH (1-34) increased tissue levels of aldosterone, cortisol, and cortisone and reduced the ratio of cortisol to cortisone. CONCLUSION: Adrenocortical hormone levels are reduced in postsurgical hypoparathyroidism, and partly restored by short-term continuous subcutaneous PTH (1-34) therapy. CLINICAL TRIAL REGISTRATION NUMBER: NCT02986607.

Investigating optimal ß-cell-preserving treatment in latent autoimmune diabetes in adults: Results from a 21-month randomized trial.

AIMS: To compare outcomes of glucagon-stimulated C-peptide tests (GSCTs) in people with latent autoimmune diabetes in adults (LADA) after a 21-month intervention with either insulin or the dipeptidyl peptidase-4 inhibitor sitagliptin. RESEARCH DESIGN AND METHODS: We included 64 glutamic acid decarboxylase (GAD) antibody-positive individuals, who were diagnosed with diabetes <3 years before the study, aged 30 to 70 years, and without clinical need for insulin treatment. We stratified participants by age and body mass index (BMI) and evaluated ß-cell function by GSCT after a 48-hour temporary withdrawal of study medication. RESULTS: Age at randomization (mean 53 years), BMI (mean 27 kg/m2 ) and metabolic markers were similar between treatment arms. Glycated haemoglobin concentrations during intervention did not differ between arms. Fasting C-peptide concentrations after the intervention were similar, as were stimulated C-peptide levels (0.82 ± 0.63 nmol/L after insulin, 0.82 ± 0.46 nmol/L after sitagliptin; nonsignificant). Autoimmunity in the study population (estimated from GAD antibody titres and positivity/no positivity for zinc transporter 8 and islet antigen 2 antibodies) affected the evolution of the GSCT results significantly, which deteriorated in participants with high but not in those with low autoimmunity. Adjustment using analysis of covariance for the degree of autoimmunity did not alter the findings of no difference between treatment arms. CONCLUSIONS: ß-cell function after intervention was similar in patients with insulin- and sitagliptin-treated LADA, regardless of the strength of autoimmunity. Further, participants with low levels of GAD antibodies did not experience progressive deterioration of ß-cell function over a 21-month period. Taken together, these findings could be useful for clinicians' choices of treatment in people with LADA.

Correction to: HbA1c versus oral glucose tolerance test as a method to diagnose diabetes mellitus in vascular surgery patients.

The authors found errors in Table 1 after publication of the original article [1].The correct values for medical history of coronary artery disease (CAD) at baseline are 110 (40%) of all patients, 54 (35.5%) of patients categorized as having normoglycaemia, 42 (46.7%) of patients categorized as having intermediate hyperglycaemia, and 14 (42.4%) of patients categorized as having DM.All presented numbers and calculations in Table 1 are checked. No other errors were found. The presented errors did not affect results, scientific content or conclusions.The corrected Table 1 is presented in this erratum.The authors apologize for having presented this error in the original article.

Epidemiology and Health-Related Quality of Life in Hypoparathyroidism in Norway.

OBJECTIVE: The epidemiology of hypoparathyroidism (HP) is largely unknown. We aimed to determine prevalence, etiologies, health related quality of life (HRQOL) and treatment pattern of HP. METHODS: Patients with HP and 22q11 deletion syndrome (DiGeorge syndrome) were identified in electronic hospital registries. All identified patients were invited to participate in a survey. Among patients who responded, HRQOL was determined by Short Form 36 and Hospital Anxiety and Depression scale. Autoantibodies were measured and candidate genes (CaSR, AIRE, GATA3, and 22q11-deletion) were sequenced for classification of etiology. RESULTS: We identified 522 patients (511 alive) and estimated overall prevalence at 102 per million divided among postsurgical HP (64 per million), nonsurgical HP (30 per million), and pseudo-HP (8 per million). Nonsurgical HP comprised autosomal dominant hypocalcemia (21%), autoimmune polyendocrine syndrome type 1 (17%), DiGeorge/22q11 deletion syndrome (15%), idiopathic HP (44%), and others (4%). Among the 283 respondents (median age, 53 years [range, 9-89], 75% females), seven formerly classified as idiopathic were reclassified after genetic and immunological analyses, whereas 26 (37% of nonsurgical HP) remained idiopathic. Most were treated with vitamin D (94%) and calcium (70%), and 10 received PTH. HP patients scored significantly worse than the normative population on Short Form 36 and Hospital Anxiety and Depression scale; patients with postsurgical scored worse than those with nonsurgical HP and pseudo-HP, especially on physical health. CONCLUSIONS: We found higher prevalence of nonsurgical HP in Norway than reported elsewhere. Genetic testing and autoimmunity screening of idiopathic HP identified a specific cause in 21%. Further research is necessary to unravel the causes of idiopathic HP and to improve the reduced HRQOL reported by HP patients.

Hypomagnesemia and functional hypoparathyroidism due to novel mutations in the Mg-channel TRPM6.

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.

HbA1c versus oral glucose tolerance test as a method to diagnose diabetes mellitus in vascular surgery patients.

BACKGROUND: The diagnosis of diabetes mellitus (DM) is based on either fasting plasma glucose levels or an oral glucose tolerance test (OGTT). Recently, an HbA1c value of ≥ 48 mmol/mol (6.5%) has been included as an additional test to diagnose DM. The purpose of this study was to validate HbA1c versus OGTT as a method to diagnose DM in vascular surgery patients. METHODS: The study population consisted of 345 patients admitted consecutively due to peripheral arterial disease. Sixty-seven patients were previously diagnosed with DM. Glucose levels of OGTT and HbA1c values were analyzed in 275 patients. The OGTT results were categorized into three groups according to the World Health Organization 1999 criteria: 1) DM defined as fasting plasma glucose (FPG) ≥ 7.0 mmol/L and/or two-hour value (2-h-value) ≥ 11.1 mmol/L; 2) intermediate hyperglycaemia, which consists of IGT (FPG < 7.0 mmol/L and a 2-h-value between 7.8 mmol/L and 11.1 mmol/L), and IFG (fasting glucose value between 6.1 mmol/L and 7.0 mmol/L with a normal 2-h-value); and 3) normal glucose metabolism defined as FPG < 6.1 mmol/L and a 2-h-value < 7.8 mmol/L. RESULTS: Of the 275 patients on whom OGTT was performed, 33 were diagnosed with DM, 90 with intermediate hyperglycaemia and 152 had normal glucose metabolism. An HbA1c value of ≥ 48 mmol/mol (6.5%) detected DM with a 45.5% sensitivity and a 90% specificity compared with the OGTT results. Combining the measurements of the HbA1c value with the fasting plasma glucose level (≥7.0 mmol/L) increased the sensitivity to 64%. The total prevalence of DM and intermediate hyperglycaemia was 85% based on HbA1c values and 45% based on the OGTT. CONCLUSIONS: Compared with the OGTT the HbA1c cut-off value of ≥ 48 mmol/mol (6.5%) had a 45.5% sensitivity to diagnose DM in patients with peripheral arterial disease. OGTT and HbA1c categorized different individuals with DM and intermediate hyperglycaemia. The total prevalence of pathologic glucose metabolism was substantially higher based on HbA1c values than based on OGTT. The high prevalence of DM and intermediate hyperglycaemia when using HbA1c in this study may reflect a high chronic glycaemic burden in patients with peripheral arterial disease. Further studies on vascular surgery patients are needed to identify which method, OGTT or HbA1c, is the better in predicting DM and future clinical development of vascular disease. TRIAL REGISTRATION: REK vest 14109.