A 55-year-old female patient presented with generalized tonic-clonic seizures. Laboratory evaluation revealed low calcium (4.9 mg/dl), low PTH (0.9 pg/ml), and positive activating CaSR antibodies. The condition was diagnosed as autoimmune hypoparathyroidism. Calcium and vitamin D supplements did not correct the patient's hypocalcemia. The addition of prednisone to vitamin supplements showed a better response and corrected the hypocalcemia. The patient remained in seizure-free for one year.

The Calcium-Sensing Receptor (CaSR) is a member of the class C of G-proteins coupled receptors (GPCRs), it plays a pivotal role in calcium homeostasis by directly controlling calcium excretion in the kidneys and indirectly by regulating parathyroid hormone (PTH) release from the parathyroid glands. The CaSR is found to be ubiquitously expressed in the body, playing a plethora of additional functions spanning from fluid secretion, insulin release, neuronal development, vessel tone to cell proliferation and apoptosis, to name but a few. The present review aims to elucidate and clarify the emerging regulatory effects that the CaSR plays in inflammation in several tissues, where it mostly promotes pro-inflammatory responses, with the exception of the large intestine, where contradictory roles have been recently reported. The CaSR has been found to be expressed even in immune cells, where it stimulates immune response and chemokinesis. On the other hand, CaSR expression seems to be boosted under inflammatory stimulus, in particular, by pro-inflammatory cytokines. Because of this, the CaSR has been addressed as a key factor responsible for hypocalcemia and low levels of PTH that are commonly found in critically ill patients under sepsis or after burn injury. Moreover, the CaSR has been found to be implicated in autoimmune-hypoparathyroidism, recently found also in patients treated with immune-checkpoint inhibitors. Given the tight bound between the CaSR, calcium and vitamin D metabolism, we also speculate about their roles in the pathogenesis of severe acute respiratory syndrome coronavirus-19 (SARS-COVID-19) infection and their impact on patients' prognosis. We will further explore the therapeutic potential of pharmacological targeting of the CaSR for the treatment and management of aberrant inflammatory responses.

This review highlights oral anomalies with major clinical impact in Addison disease (AD), including dental health and dermatologic features, through a dual perspective: pigmentation issues and AD comorbidities with oral manifestations. Affecting 92% of AD patients, cutaneomucosal hyperpigmentation is synchronous with or precedes general manifestations by up to a decade, underlying melanocytic infiltration of the basal epidermal layer; melanophages in the superficial dermis; and, rarely, acanthosis, perivascular lymphocytic infiltrate, and hyperkeratosis. Intraoral pigmentation might be the only sign of AD; thus, early recognition is mandatory, and biopsy is helpful in selected cases. The buccal area is the most affected location; other sites are palatine arches, lips, gums, and tongue. Pigmented oral lesions are patchy or diffuse; mostly asymptomatic; and occasionally accompanied by pain, itchiness, and burn-like lesions. Pigmented lingual patches are isolated or multiple, located on dorsal and lateral areas; fungiform pigmented papillae are also reported in AD individuals. Dermoscopy examination is particularly indicated for fungal etiology; yet, it is not routinely performed. AD's comorbidity burden includes the cluster of autoimmune polyglandular syndrome (APS) type 1 underlying AIRE gene malfunction. Chronic cutaneomucosal candidiasis (CMC), including oral CMC, represents the first sign of APS1 in 70-80% of cases, displaying autoantibodies against interleukin (IL)-17A, IL-17F ± IL-22, and probably a high mucosal concentration of interferon (IFN)-γ. CMC is prone to systemic candidiasis, representing a procarcinogenic status due to Th17 cell anomalies. In APS1, the first cause of mortality is infections (24%), followed by oral and esophageal cancers (15%). Autoimmune hypoparathyroidism (HyP) is the earliest endocrine element in APS1; a combination of CMC by the age of 5 years and dental enamel hypoplasia (the most frequent dental complication of pediatric HyP) by the age of 15 is an indication for HyP assessment. Children with HyP might experience short dental roots, enamel opacities, hypodontia, and eruption dysfunctions. Copresence of APS-related type 1 diabetes mellitus (DM) enhances the risk of CMC, as well as periodontal disease (PD). Anemia-related mucosal pallor is related to DM, hypothyroidism, hypogonadism, corresponding gastroenterological diseases (Crohn's disease also presents oral ulceration (OU), mucogingivitis, and a 2-3 times higher risk of PD; Biermer anemia might cause hyperpigmentation by itself), and rheumatologic diseases (lupus induces OU, honeycomb plaques, keratotic plaques, angular cheilitis, buccal petechial lesions, and PD). In more than half of the patients, associated vitiligo involves depigmentation of oral mucosa at different levels (palatal, gingival, alveolar, buccal mucosa, and lips). Celiac disease may manifest xerostomia, dry lips, OU, sialadenitis, recurrent aphthous stomatitis and dental enamel defects in children, a higher prevalence of caries and dentin sensitivity, and gingival bleeding. Oral pigmented lesions might provide a useful index of suspicion for AD in apparently healthy individuals, and thus an adrenocorticotropic hormone (ACTH) stimulation is useful. The spectrum of autoimmune AD comorbidities massively complicates the overall picture of oral manifestations.

Systemic lupus erythematosus (SLE) is an autoimmune disease and may be associated with many autoimmune conditions. Hypoparathyroidism is a rare disease. The leading cause of hypoparathyroidism is postsurgical hypoparathyroidism. However, hypoparathyroidism as an initial presentation of SLE is still a rare condition. Here, we report a case of SLE presented with hypoparathyroidism and Hashimoto's thyroiditis.

Hypoparathyroidism is considered a rare endocrine disease. Despite being a deficiency of parathyroid hormone, the standard therapy is based on oral calcium and active vitamin D supplementation. This approach provides satisfactory management in most cases but may be inadequate for patients in the most complex spectrum of the disease. Other therapies are being explored, and among them, the use of recombinant human parathyroid hormone (PTH) has proved to decrease the requirements of calcium and active vitamin D to reach adequate therapeutic goals. We aimed to provide information on the effectiveness of the current recombinant parathyroid hormone analogs in the clinical management of difficult to control cases of hypoparathyroidism. We report our experience using teriparatide and PTH (1-84) through five complex cases of hypoparathyroidism of diverse etiologies. We describe each case and report the effectiveness of treatment in clinical practice. Four patients with postsurgical hypoparathyroidism and one patient with autoimmune hypoparathyroidism, all of them with suboptimal control under the standard treatment with calcium and calcitriol supplements or calcium gluconate infusion, are presented. They were all started on teriparatide or PTH (1-84), and all of them showed a diminishment of symptoms and were able to maintain normocalcemia without parenteral calcium despite a reduction of oral treatment. This article highlights the effectiveness and safety of hormonal replacement treatment in difficult to manage hypoparathyroidism and provides evidence which justifies its off-label prescription in the case of teriparatide. We consider that this treatment should be considered in cases in which standard treatment fails to reach adequate therapeutic goals.