Hypoparathyroidism-Retardation-Dysmorphism Syndrome due to a Variant in the Tubulin-Specific Chaperone E Gene as a Cause of Combined Immune Deficiency.

BACKGROUND: Hypoparathyroidism-retardation-dysmorphism (HRD) syndrome is a disease composed of hypoparathyroidism, growth retardation, severe developmental delay, and typical dysmorphic features caused by the tubulin-specific chaperone E gene variant. Many patients succumb in infancy to HRD due to overwhelming infections mainly caused by Pneumococcus spp. Knowledge related to the immune system in these patients is scarce. PURPOSE: To define the immune phenotype of a cohort of HRD patients including their cellular, humoral, and neutrophil functions. METHODS: The study included HRD patients followed at Soroka University Medical Center. Clinical and immunological data were obtained, including immunoglobulin concentrations, specific antibody titers, lymphocyte subpopulations, lymphocyte proliferation, and neutrophil functions. RESULTS: Nine patients (5 females and 4 males) were enrolled, aged 6 months to 15 years. All received amoxicillin prophylaxis as part of a routine established previously. Three patients had bacteremia with Klebsiella, Shigella spp., and Candida. Three patients had confirmed coronavirus disease 19 (COVID-19), and two of them died from this infection. All patients had normal blood counts. Patients showed high total IgA and IgE levels, low anti-pneumococcal antibodies in spite of a routine vaccination schedule, and reduced frequency of naive B cells with increased frequency of CD21lowCD27- B cells. All patients had abnormal T-cell population distributions, including reduced terminally differentiated effector memory CD8, inverted CD4/CD8 ratios, and impaired phytohemagglutinin (PHA)-induced lymphocyte proliferation. Neutrophil superoxide production and chemotaxis were normal in all patients tested. CONCLUSION: HRD is a combined immunodeficiency disease with syndromic features, manifesting in severe invasive bacterial and viral infections.

Unrecognized Primary Hypoparathyroidism with Severe Hypocalcemia in the Presence of COVID-19 Infection.

Primary hypoparathyroidism (PHPT) is a rare disease most commonly caused by surgical parathyroid glands destruction or genetic disorders. PHPT manifestation varies from subclinical to acute or even lethal symptoms. In atypical presentation the signs of hypocalcemia could be missed, and asymptotic chronic hypocalcemia could manifest only in the presence of exacerbated comorbidities, infections, hypomagnesemia or certain medications. We present a case of PHPT with severe hypocalcemia manifesting as seizures and delirium in a presence of COVID-19 infection.

Fahr's Syndrome for Primary Hypoparathyroidism in a Patient With COVID-19.

Fahr's syndrome, recently named "primary brain calcification," is a rare disorder with a variable clinical presentation ranging from behavioral changes to seizures. It can be idiopathic or have multiple causes, hypoparathyroidism the most frequent. In the current coronavirus 2019 (COVID-19) pandemic, these electrolyte imbalances have acquired importance, and there has been a correlation between the lowest serum calcium levels and severe COVID-19 disease. It is known that calcium accomplishes many normal physiologic functions. We present a case of a 63-year-old woman who arrived at the emergency room with a fever of 10-day duration, odynophagia, dry cough, dyspnea, and drowsiness. Upon her arrival, computed tomography of the brain and chest was performed, showing areas of calcification in the basal nuclei and infiltrates with a ground-glass pattern, respectively. In addition, laboratory studies were conducted in which hypocalcemia and hyperphosphatemia stand out. Furthermore, a positive result was obtained from acute Respiratory Syndrome Coronavirus 2 (SARS-COV2) from bronchial secretion. According to the clinical presentation data in the imaging and laboratory studies, Fahr's syndrome and COVID-19 pneumonia were diagnosed. We consider evaluating electrolyte imbalances at case presentations essential and continuously monitoring them. Appropriate and prompt corrections were achieved in patients with hypoparathyroidism history and severe COVID-19 disease. This case shows the vital collaboration between endocrinologists and other physicians that care for patients with COVID-19 infection.

Hypocalcemia in hospitalized patients with COVID-19: roles of hypovitaminosis D and functional hypoparathyroidism.

INTRODUCTION: Despite the high prevalence of hypocalcemia in patients with COVID-19, very limited studies have been designed to evaluate etiologies of this disorder. This study was designed to evaluate the status of serum parameters involved in calcium metabolism in patients with COVID-19 and hypocalcemia. MATERIALS AND METHODS: This cross-sectional study was conducted on 123 hospitalized patients with COVID-19. Serum concentrations of PTH, 25 (OH) D, magnesium, phosphate, and albumin were assessed and compared across three groups of moderate/severe hypocalcemia (serum total calcium < 8 mg/dl), mild hypocalcemia (8 mg/dl ≤ serum total calcium < 8.5 mg/dl) and normocalcemia (serum total calcium ≥ 8.5 mg/dl). Multivariate analyses were performed to evaluate the independent roles of serum parameters in hypocalcemia. RESULTS: In total, 65.9% of the patients had hypocalcemia. Vitamin D deficiency was found in 44.4% and 37.7% of moderate/severe and mild hypocalcemia cases, respectively, compared to 7.1% in the normal serum total calcium group (P = 0.003). In multivariate analysis, vitamin D deficiency was independently associated with 6.2 times higher risk of hypocalcemia (P = 0.001). Only a minority of patients with hypocalcemia had appropriately high PTH (15.1% and 14.3% in mild and moderate/severe hypocalcemia, respectively). Serum PTH was low/low-normal in 40.0% of patients with moderate/severe low-corrected calcium group. Magnesium deficiency was not associated with hypocalcemia in univariate and multivariate analysis. CONCLUSION: Vitamin D deficiency plays a major role in hypocalcemia among hospitalized patients with COVID-19. Inappropriately low/low-normal serum PTH may be a contributing factor in this disorder.

COVID-19 induced hypoparathyroidism: A case report.

Low levels of serum calcium, elevated levels of serum phosphorus and absent or abnormally low levels of serum parathyroid hormone characterize hypoparathyroidism, a rare endocrine deficiency illness. Hypoparathyroidism is caused by injury to the parathyroid gland as a result of surgery or autoimmune disease. In addition, hypoparathyroidism may develop due to genetic causes or infiltrative diseases. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by multi-organ involvement, including the dysfunction of endocrine glands. Previous studies have demonstrated that SARS-CoV-2 infection induces endocrine tissue damage via various mechanisms, including direct cell damage from viral entry to the glands by binding to the angiotensin converting enzyme 2 receptors and replication, vasculitis, arterial and venous thrombosis, hypoxic cell damage, immune response and the cytokine storm. The effects of the new coronavirus, coronavirus disease 2019 (COVID-19) on the parathyroid glands have received limited attention. Hypoparathyroidism has been observed in a small number of individuals as a result of SARS-CoV-2 infection. The present study describes the case of a patient with primary hypoparathyroidism induced by COVID-19. Clinicians should also keep in mind that, despite the fact that SARS-CoV-2 has no known tropism for the parathyroid glands, it can result in primary hypoparathyroidism and decompensation of old primary hypoparathyroidism.

Good Clinical Practice of the Italian Society of Thalassemia and Haemoglobinopathies (SITE) for the Management of Endocrine Complications in Patients with Haemoglobinopathies.

BACKGROUND: The treatment of endocrinopathies in haemoglobinopathies is a continually expanding research area; therefore, recommendations supporting the appropriateness of treatments are a pressing need for the medical community. METHODS: The Management Committee of SITE selected and gathered a multidisciplinary and multi-professional team, including experts in haemoglobinopathies and experts in endocrinopathies, who have been flanked by experts with methodological and organizational expertise, in order to formulate recommendations based on the available scientific evidence integrated by personal clinical experience. The project followed the systematic approach for the production of clinical practice guidelines according to the methodology suggested by the National Center for Clinical Excellence, Quality and Safety of Care (CNEC). RESULTS: Out of 14 topics, 100 clinical questions were addressed, and 206 recommendations were elaborated on. The strength of recommendations, panel agreement, a short general description of the topic, and the interpretation of evidence were reported. CONCLUSIONS: Good Practice Recommendations are the final outcome of translational research and allow one to transfer to the daily clinical practice of endocrine complications in haemoglobinopathies.

Management of Parathyroid Disease during the COVID-19 Pandemic.

The coronavirus disease, COVID-19, has caused widespread and sustained disruption to healthcare, not only in the delivery of emergency care, but knock-on consequences have resulted in major delays to the delivery of elective care, including surgery. COVID-19 has accelerated novel pathways for delivering clinical services, many of which have an increased reliance on technology. COVID-19 has impacted care for patients with both hypoparathyroidism and hyperparathyroidism. The role of vitamin D in the prevention of severe COVID-19 infection has also been widely debated. Severe hypocalcemia can be precipitated by infection in patients with hypoparathyroidism. With this in mind, compliance with medical management, including calcium and vitamin D supplementation, is crucial. Technology in the form of text message reminders and smartphone apps may have a key role in ensuring this. Furthermore, clinicians should ensure that patients are educated on the symptoms of hypocalcemia and the steps needing to be taken should these symptoms be experienced. Patients with primary hyperparathyroidism (PHPT) should be educated on the symptoms of hypercalcemia, as well as the importance of remaining adequately hydrated. In addition, patients should be reassured that the postponement of parathyroidectomy is likely to have negligible impact on their condition; for those with symptomatic hypercalcemia, cinacalcet can be considered as an interim measure.

Fahr's syndrome presenting with seizures in SARS-CoV-2 (COVID-19) pneumonia-a case report.

BACKGROUND: Fahr's syndrome (or Fahr's disease) is a rare, neurological disorder characterized by bilateral calcification in the cerebellum, thalamus, basal ganglia, and cerebral cortex as a result of calcium and phosphorus metabolism disorder. The patients may be asymptomatic and clinical symptoms represent a wide range of neurologic manifestations and nonspecific neuropsychiatric disorders. We report an unusual case of Fahr's syndrome which was asymptomatic and incidentally diagnosed by generalized tonic-clonic seizure in a patient with SARS-CoV-2 (COVID-19) pneumonia. CASE PRESENTATION: The patient was a 68-year-old female and admitted to our emergency department suffering from cough and fatigue. After thorax computed tomography (CT) and SARS-CoV-2 PCR test, she was diagnosed as COVID-19 pneumonia. In the intensive care unit, the patient had a tonic-clonic convulsion starting from the left arm and spreading to the whole body. Fahr's syndrome was diagnosed after a cranial CT scan and blood metabolic panel test. CONCLUSIONS: As a result of the clinical, radiological, and biochemical evaluations, the patient was diagnosed incidentally as Fahr's syndrome associated with hypoparathyroidism. Seizures could be induced by hydroxychloroquine that was in the COVID-19 treatment or the inflammation caused by COVID-19 pneumonia. The association between the mortality of COVID-19 pneumonia and Fahr's syndrome is unknown which needs further research.

A Novel Case of Hypoparathyroidism Secondary to SARS-CoV-2 Infection.

Hypoparathyroidism is usually caused by postsurgical or autoimmune damage to the parathyroid gland. We present the case of a 46-year-old Hispanic male with no significant past medical history who was admitted to the hospital with hypoxic respiratory failure due to coronavirus disease 2019 (COVID-19) infection and had a prolonged hospital course. He was incidentally found to have hyperphosphatemia and low parathyroid hormone (PTH) levels. During the second month of hospitalization, his phosphorus levels rose to 6.9 mg/dL (normal range: 2.4-4.7 mg/dl). His PTH levels were found to be at 8 pg/mL. Vitamin D levels obtained were also low (7 ng/dL), phosphorus was at 5.8 mg/dL with albumin of 2.9 g/dL, and calcium level was normal at 9.2 mg/dl. Parathyroid hormone-related peptide (PTHrP) level was low at 10. Malignancy and genetic causes were ruled out. The patient was started on 50,000 units of ergocalciferol once a week. He was also started on calcium acetate 1,334 mg three times a day for hyperphosphatemia. Phosphorus levels remained elevated, and sevelamer was added on discharge after he was weaned off oxygen and cleared by physical therapy. No explanation for persistent hyperphosphatemia and hypoparathyroidism was found. To date, there have been some reports linking severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to widespread tissue injury; however, there have been no reports so far on the effect of the parathyroid gland. Further studies are necessary to elaborate and to confirm the causative relationship between SARS-CoV-2 and hyperphosphatemia.