Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research

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.

FIG. 1

A clinical algorithm for the workup of the patient who presents with hypocalcemia, which should be confirmed with a repeat measurement, along with the specific steps in the workup to confirm the diagnosis of hypoparathyroidism. Additional etiologies for hypoparathyroidism are discussed in greater detail in the text, to which the reader is referred for further reference, and definitive genetic testing resources for explicit diagnoses and mutational analysis should be researched by the treating clinician or a geneticist.

FIG. 2

Relationship between parathyroid hormone (PTH) structure, PTH assay generations, known PTH assay epitopes, and known circulating PTH molecular forms. With each generation, PTH assays have become more selective toward full-length PTH(1-84).

FIG. 3

Images showing tissue stress levels under axial loading generated by microfinite element analysis based on microcomputed tomography of iliac crest bone biopsies (A, C, E) and high-resolution peripheral quantitative computed tomography (B, D, F) of the radius in a premenopausal woman with idiopathic osteoporosis (A and B), a normal premenopausal control (C and D), and a patient with hypoparathyroidism (E and F). Dark blue indicates the regions with lowest stress, and dark red indicates the regions with highest stress. The lowest stress levels are seen in the subject with hypoparathyroidism. Reproduced with permission.⁽⁹⁵⁾

FIG. 4

Reconstructed remodeling cycles in hypoparathyroid (upper) and normal (lower) subjects. Note the marked elongation of all phases of the remodeling cycle in hypoparathyroidism. Reproduced with permission.⁽⁹⁵⁾

FIG. 5

Low-power view of iliac crest bone biopsies from a control subject (left) and a subject with hypoparathyroidism (right). Goldner trichrome stain. Note the increase in cancellous bone volume and cortical thickness in the hypoparathyroid subject. Reproduced with permission from.⁽⁹⁴⁾

FIG. 6

Cancellous and cortical bone parameters obtained by histomorphometry in subjects with hypoparathyroidism (hatched bars) and controls (open bars). Values are mean±SD. Drawn from data from Rubin et al.⁽⁹⁴⁾

FIG. 7

Tetracycline labels in a hypoparathyroid (left) and control subject (right). Tetracycline uptake was markedly reduced in the hypoparathyroid subject, reflecting the low turnover rate.

FIG. 8

Reconstructed microcomputed tomographic images of cancellous bone from a hypoparathyroid (left) and a control subject (right). Note the dense trabecular structure in hypoparathyroidism. Reproduced with permission.⁽⁹⁷⁾

FIG. 9

Changes in calcium and 1,25-dihydroxyvitamin D supplementation: Calcium requirements decreased at 3, 9, 12, 18, and 24 months from baseline while 1,25-dihydroxyvitamin D requirements decreased by 1 month. Data are mean±SD. *P<.05 as comparison to baseline. Reproduced with permission.⁽¹⁴⁶⁾

FIG. 10

Changes in serum calcium, serum phosphate, and urinary calcium: Serum calcium increased at Months 2 through 6 but was no different from baseline at 1, 9, 12, 18, and 24 months. Serum phosphate decreased into the normal range at Month 3 and remained in the normal range through 24 months. The shaded area shows the normal ranges of serum calcium and phosphate. Urinary calcium increased at 3 months but otherwise did not change. The heavier and lighter dashed lines show the upper limit of normal urinary calcium levels in men and women, respectively. Data are mean±SD. *P<.05 as comparison to baseline. Reproduced with permission.⁽¹⁴⁶⁾

FIG. 11

Changes in bone mineral density (BMD): Lumbar spine BMD increased, while the femoral neck did not change and the distal 1/3 radius BMD decreased. Data are mean ± SD. *P<.05 as comparison to baseline. Reproduced with permission.⁽¹⁴⁶⁾