[Hypoparathyroidism: the present state of art]. / Niedoczynnosc przytarczyc: wspólczesny stan wiedzy.

Hypoparathyroidism is a result of reduced secretion or impaired action of parathyroid hormone (PTH). Although considered a rare condition, hypoparathyroidism seems to occur much more frequently than reported. In most cases, hypoparathyroidism remains a complication of neck surgery. However, there is a growing incidence of the autoimmune form of hypoparathyroidism, which may occur in combination with other autoimmune diseases. As parathyroid glands are necessary to sustain life and maintain homeostasis, undetected or misdiagnosed hypoparathyroidism may pose a significant threat to health outcomes, as its presence may increase morbidity and mortality in affected individuals. The clinical consequences of PTH deficiency or impaired receptor action are multidirectional and include nervous hyperexcitability, paresthesias, cramps, tetany, hyperreflexia, convulsions, cataract, weakened tooth enamel, brittle nails and basal ganglia calcifications. In some patients, however, its manifestation may be non-specific, and in these cases the correct diagnosis may be easily missed. Laboratory measurements show hypocalcemia, hyperphosphatemia, and, with the exception of pseudohypoparathyroidism, inappropriately low or undetectable PTH levels. Treatment consists of oral calcium supplementation and vitamin D derivatives. In this review article, we discuss the causes, clinical picture, diagnosis and treatment of hypoparathyroidism and provide the reader with some practical guidance concerning dealing with a patient suffering from this disorder.

[Parathyroid hormone for disorders of calcium metabolism and metabolic bone diseases other than osteoporosis].

Recombinant human parathyroid hormone (PTH) analogues reduce fractures in patients with osteoporosis by enhancing bone formation and improving bone quality. Furthermore, many studies have demonstrated the efficacy of these analogues in diseases such as PTH-deficient hypoparathyroidism, bisphosphonate-related osteonecrosis of the jaw and hypophosphatasia. Further studies are needed to examine the long-term effects and the safety of these analogues in children and cancer patients.

Clinical data analysis of 22 cases with hypoparathyroidism misdiagnosed as epilepsy.

OBJECTIVE: Patients with hypoparathyroidism always present with recurrent tetany caused by hypocalcemia. These patients are usually misdiagnosed with epilepsy and incorrectly treated with anti-epileptic drugs. This research analyzed clinical data about 22 patients with hypoparathyroidism misdiagnosed as epilepsy and summarized the clinical experience for reducing misdiagnosis and incorrect therapy about hypoparathyroidism. METHOD: Totally 160 patients with hypoparathyroidism, administrated to the First Medical Center of Chinese PLA General Hospital from January 1st, 2008, to July 1st, 2021, were enrolled in this report. Clinical data about 22 patients initially misdiagnosed with epilepsy were analyzed. RESULTS: Of the 160 cases with hypoparathyroidism, 22 patients (12 males and 10 females) were misdiagnosed with epilepsy in local hospitals. The misdiagnosis rate was 13.75% and the median duration of misdiagnosis was 8.0 (2.0, 14.8) years. The clinical manifestations of the 22 patients misdiagnosed as epilepsy included tetany 81.8% (18/22), disturbance of consciousness 27.3% (6/22), limb numbness 13.6% (3/22), limb weakness 27.3% (6/22), mental and behavioral abnormality 9.1% (2/22), and memory impairment 13.6% (3/22), etc. Electroencephalogram (EEG) was performed in 9 cases, which presented as slow wave and spike-slow complex wave in 3 cases, slowing down of Î¸ and δ band background in 2 cases and normal EEG in 4 cases. Out of the 15 cases that underwent head computed tomography (CT) scan, in which 13 cases had intracranial calcification. Anti-epileptic drugs were used to treat 22 patients, of which 17 patients were treated with two kinds of drugs. With calcium and calcitriol supplement in all these 22 patients, the anti-epileptic drugs were gradually reduced and withdrawn in 17 cases. In the other 5 cases with secondary epilepsy, the type of anti-epileptic drugs was reduced to one and the clinical condition improved obviously. CONCLUSION: The clinical manifestations of hypoparathyroidism are complex and usually be misdiagnosed as primary epilepsy. Detection of serum calcium, phosphorus and parathyroid hormone is very important to avoid misdiagnosis and incorrect therapy about hypoparathyroidism.

[A case of adult-onset spike-wave stupor associated with hypoparathyroidism and hyperostosis frontalis interna (HFI)].

A 34-year-old women without history of seizures was admitted to our hospital because of the diminished responsiveness and the repeated blinking for two days. Her past history showed neither surgery nor inflammation of the thyroid gland. General physical examination was normal. On neurological examination, the patient was blinking frequently and staring without any responsiveness. However, she occasionally became able to respond correctly to verbal orders, such as "open your eyes", "open your mouth", "stand up" and so on, which occurred abruptly just like the switch-on. She was otherwise normal neurologically. The laboratory data showed hypocalcemia, hyperphosphatemia, decreased level of parathyroid hormone and normal renal function, indicating the presence of idiopathic hypoparathyroidism. EEG showed the continuous generalized 2-4 Hz spike and wave complexes with the maximum intensity on frontal lobes. Skull roentgenograms and MRI CT of the head disclosed hyperostosis frontalis interna (HFI) and the compression of superior medial frontal lobes by the HIF. SPECT also showed the diminished circulation and hypometabolism in the superior frontal lobes. Based on clinical and EEG findings, the diagnosis of spike-wave stupor was made. She was successfully treated with valproic acid and ethosuximide. Spike and wave complexes on EEG completely disappeared after administration of alfacalcidole. It is assumed that both hypoparathyroidism and HFI were deeply involved in the development of spike-wave stupor in this adult case.

Development of PTH eluting microspheres for the treatment of hypoparathyroidism.

BACKGROUND: Parathyroid hormone (PTH) replacement has been demonstrated to be superior to conventional treatment with calcium supplementation and vitamin D analogs for the treatment of hypoparathyroidism. In this investigation we evaluated the feasibility of using PTH microsphere encapsulation as a potential delivery system for PTH. MATERIALS AND METHODS: Using the spontaneous emulsion technique, PTH microspheres were created by encapsulating PTH (1-34) in a copolymer of polyglycolic and polylactic acid (PLGA). Additional microspheres were constructed by coencapsulating calmodulin with PTH (1-34) in the PLGA microspheres. Microsphere production was confirmed using electron microscopy. PTH release was measured in vitro using an enzyme-linked immunosorbent assay. The bioactivity of PTH released from the microspheres was confirmed in vivo using a hypoparathyroid rat model by measuring serum calcium concentrations before and 3 h after subcutaneous injection of PTH microspheres. RESULTS: PTH microsphere and PTH/calmodulin microspheres could be created using the spontaneous emulsion technique. Physiologically significant PTH release was measured in vitro for 20 days. PTH release was calcium sensitive and exhibited negative feedback. This effect was augmented by coencapsulation with calmodulin. PTH released from the microspheres caused a significant rise in serum calcium levels from an average of 6.35 (6.19-6.48 mg/dL) to 8.55 mg/dL (8.22-8.73). PTH released from the PTH/calmodulin microspheres resulted in an increase in serum calcium from a mean of 6.8 (6.7-6.9 mg/dL) to 8.1 mg/dL (7.8-8.2). CONCLUSIONS: The PLGA microspheres can be used to provide calcium sensitive controlled release of biologically active PTH and offer a potential mean of providing biomimetic hormone replacement therapy.

Development of a parathyroid hormone-controlled release system as a potential surgical treatment for hypoparathyroidism.

BACKGROUND/PURPOSE: The aim of this study was to develop a surgically implantable controlled release delivery system for parathyroid hormone (PTH) that will maintain calcium homeostasis without the adverse side effects of long-term calcium and vitamin D replacement and can be used for the treatment of hypoparathyroidism. METHODS: Biodegradable poly(lactide-co-glycolide) (PLGA) microspheres loaded with PTH were made using a modification of the double emulsion (water/oil/water) solvent evaporation technique. To simulate the release of PTH from microspheres after implantation in an animal, the in vitro release profile for the PTH microspheres was determined by incubating the PTH microspheres in phosphate-buffered saline, serially sampling the effluent, and determining the concentration of PTH in the effluent over time using an enzyme-linked immunosorbent assay. RESULTS: (1) PTH was successfully incorporated into PLGA microspheres. (2) Controlled release of PTH was demonstrated in vitro over a 3-week period. (3) Release of physiological significant concentrations of PTH was achieved using this methodology. CONCLUSIONS: Controlled release of physiological concentrations of PTH can be achieved using PLGA microsphere encapsulation.