Management of Hypoparathyroidism.

Hypoparathyroidism (HypoPT) is a rare disorder characterized by hypocalcemia in the presence of a low or inappropriately normal parathyroid hormone level. HypoPT is most commonly seen after neck surgery, which accounts for approximately 75% of cases, whereas approximately 25% have HypoPT due to nonsurgical causes. In both groups of patients, conventional therapy includes calcium and active vitamin D analogue therapy aiming to maintain serum calcium concentration in the low normal or just below the normal reference range and normalize serum phosphorus, magnesium concentrations, and urine calcium levels. The limitations of conventional therapy include wide fluctuations in serum calcium, high pill burden, poor quality of life, and renal complications. Parathyroid hormone (PTH) replacement therapy may improve the biochemical profile in those in whom conventional therapy proves unsatisfactory. Based on a systematic review and meta-analysis of the literature, the panel made a graded recommendation suggesting conventional therapy as first line therapy rather than administration of PTH (weak recommendation, low quality evidence). When conventional therapy is deemed unsatisfactory, the panel considers use of PTH. Because pregnancy and lactation are associated with changes in calcium homeostasis, close monitoring is required during these periods with appropriate adjustment of calcium and active vitamin D analogue therapy to ensure that serum calcium remains in the mid to low normal reference range in order to avoid maternal and fetal complications. Emerging therapies include molecules with prolonged PTH action as well as different mechanisms of action that may significantly enhance drug efficacy and safety. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Initial Assessment and Monitoring of Patients with Chronic Hypoparathyroidism: A Systematic Current Practice Survey.

Chronic hypoparathyroidism (HypoPT) is associated with significant morbidity and impaired quality of life (QoL). The goals of management for chronic HypoPT include improvement in QoL and the prevention of both hypo- and hypercalcemia symptoms and long-term complications. Several groups have provided consensus statements and guidelines on the management of HypoPT; however, due to limited evidence, these recommendations have largely been based on literature reviews, expert opinion, and consensus statements. The objective of this study was to use a systematic approach to describe current practice for the initial assessment and follow-up of patients with chronic HypoPT. We developed a survey asking experts in the field to select the responses that best reflect their current practice. The survey found no differences in responses between nonsurgical and postsurgical patient assessment. For new patients, respondents usually performed an assessment of serum lab profile (calcium [either albumin-adjusted or ionized], magnesium, creatinine, phosphate, 25-hydroxyvitamin D), 24-hour urine (creatinine, calcium), and a renal ultrasound to evaluate for the presence of nephrocalcinosis or nephrolithiasis. For follow-up patients, most respondents perform blood tests and urine tests every 6 months or less frequently. The reported clinical practice patterns for monitoring for complications of chronic HypoPT vary considerably among respondents. Based on the responses in this systematic expert practice survey, we provide practice suggestions for initial assessment and follow-up of patients with chronic HypoPT. In addition, we highlight areas with significant variation in practice and identify important areas for future research. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Canadian national hypoparathyroidism registry: an overview of hypoparathyroidism in Canada.

PURPOSE: To evaluate the epidemiology, presentation and management of hypoparathyroidism in Canada. Hypoparathyroidism is associated with significant morbidity and poor quality of life. We present baseline results from the Canadian National Hypoparathyroidism Registry, a prospective observational study evaluating hypoparathyroidism in Canada. METHODS: Our study enrolled 130 patients with hypoparathyroidism. Patients were followed every 6 months with clinical and lab assessments. We present baseline data in this manuscript. RESULTS: Seventy percent (91/130) of patients had postsurgical hypoparathyroidism, 30% (39/130) of patients had nonsurgical hypoparathyroidism due to autoimmune, genetic or idiopathic causes, and a molecular diagnosis was confirmed in 11 of these 39 patients. Pseudohypoparathyroidism was confirmed in 4/39 patients, DiGeorge syndrome in 2/39 patients, Barakat syndrome with a mutation in the GATA3 gene in 1/39, and activating mutations of the CASR gene in 3/39 patients with nonsurgical hypoparathyroidism. Renal complications with nephrocalcinosis or nephrolithiasis were present in 27% (14/52) of patients with postsurgical disease and 17% (4/24) of patients with nonsurgical hypoparathyroidism. Basal ganglia calcification was noted on imaging in 15% (n = 5/34) of patients with postsurgical hypoparathyroidism and 37% (n = 7/19) of patients with nonsurgical hypoparathyroidism. CONCLUSIONS: Hypercalciuria was more commonly seen in those with renal complications of nephrocalcinosis, nephrolithiasis or CKD, and hyperphosphatemia was more commonly seen in those with basal ganglia calcification. Hospitalization occurred in 28% of those with postsurgical hypoparathyroidism and 46% of those with nonsurgical hypoparathyroidism. Hypoparathyroidism is associated with significant morbidity. Effective strategies to reduce the short-and long-term complications of hypoparathyroidism need to be developed and evaluated.

Two cases of malignant struma ovarii with metastasis to pelvic bone.

Histologically, malignant struma ovarii metastasizes rarely, and only a few cases reported bone metastasis. Here, we describe 2 cases of biologically malignant struma ovarii with pelvic bone metastasis. Case 1 is a 22-year-old female who was found to have a large left ovarian mass during routine prenatal ultrasound. Papillary thyroid cancer arising in struma ovarii was identified after laparoscopic salpingo-oophorectomy. After total thyroidectomy, radioactive iodine whole-body scan revealed extrathyroidal iodine uptake in left anterior pelvis. Subsequent I-131 treatment resolved the pelvic metastasis. Case 2 is a 49-year-old female who was diagnosed with malignant struma ovarii in 1996 and presented in 2007 with pelvic recurrence and extensive left hip metastasis. Treatment with resection of the pelvic tumor, total thyroidectomy, and multiple I-131 ablation led to eventual resolution of the abdominal and left hip foci. In conclusion, we present 2 rare cases of malignant struma ovarii, both with metastasis to the pelvic bone. This report makes pelvic bone the most frequent site for bone metastasis in malignant struma ovarii. It also emphasizes the importance of total thyroidectomy in allowing identification and treatment of bony metastasis with radioactive iodine.

Hypercalcemia in two patients with sarcoidosis and Mycobacterium avium intracellulare not mediated by elevated vitamin D metabolites.

INTRODUCTION: To describe 2 unusual cases of hypercalcemia due to granulomatous diseases with normal vitamin D metabolites and no other ready explanation for the hypercalcemia. METHODS: We present the clinical, laboratory and pathologic findings of 2 patients with hypercalcemia and review previous reports of hypercalcemia in granulomatous diseases without elevated vitamin D metabolites. RESULTS: Hypercalcemia was described in various granulomatous diseases including sarcoidosis, tuberculosis, berylliosis, leprosy and, rarely, in fungal infections. Elevated serum level of vitamin D or its metabolites was linked to the pathogenesis of hypercalcemia in these disorders. The authors present the clinical, laboratory and pathologic findings in 2 patients who presented with hypercalcemia and normal vitamin D metabolites with no other ready explanation for the hypercalcemia. The first patient was diagnosed with Mycobacterium avium, whereas the second patient was found to have sarcoidosis. CONCLUSION: Although hypercalcemia in granulomatous diseases has been attributed to be mediated by elevated vitamin D metabolites, there have been several case reports that documented normal values of active vitamin D metabolites. This report illustrates the regulatory feedback mechanisms of vitamin D synthesis and introduces the term "inappropriately normal" vitamin D metabolites levels in light of low levels of parathyroid hormone.

Effect of aging on glucose homeostasis: accelerated deterioration of beta-cell function in individuals with impaired glucose tolerance.

OBJECTIVE: To examine the effect of aging on insulin secretion (first- and second-phase insulin release) and insulin sensitivity in people with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: First- and second-phase insulin secretion and insulin sensitivity were assessed in hyperglycemic clamp experiments in 266 individuals with NGT and 130 individuals with IGT, ranging in age from approximately 20 to approximately 70 years. Changes in beta-cell function were compared using the disposition index to adjust for differences in insulin sensitivity. RESULTS: As expected, both phases of insulin release and insulin sensitivity were reduced in individuals with IGT (all P < 0.01). Insulin sensitivity was not independently correlated with age in either group. In people with NGT, the disposition index for first- and second-phase insulin release decreased similarly at a rate of approximately 0.7% per year. In people with IGT, the disposition indexes for first- and second-phase insulin release decreased at greater rates ( approximately 2.2 and 1.4% per year, P = 0.002 and 0.009, respectively, vs. NGT), with the decrease in first phase being greater than that of second phase (P = 0.025). CONCLUSIONS: Insulin secretion (both first and second phase) normally decreases at a rate of approximately 0.7% per year with aging; this decrease in beta-cell function is accelerated about two-fold in people with impaired glucose tolerance-first phase to a greater extent than second phase. Finally, aging per se has no effect on insulin sensitivity independent of changes in body composition.