Materiały źródłowe

• #1 Hypoparathyroidism – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441899/

  Hypoparathyroidism is an uncommon endocrine abnormality in which parathyroid gland dysfunction causes parathyroid hormone deficiency. […] Hypoparathyroidism is typically diagnosed with laboratory studies confirming a low corrected calcium level as well as a decreased or undetectable parathyroid hormone level. Other findings that support this diagnosis include elevated serum phosphorus, decreased 1,25-dihydroxyvitamin D, and elevated urinary fractional calcium excretion levels. […] The secretion of the parathyroid hormone is inversely related to the concentration of ionized calcium in the extracellular fluid. The activity of the calcium-sensing receptor (CaSR), a G-protein coupled receptor, is affected by calcium concentration changes. As the calcium concentration in the extracellular fluid increases, this receptor is activated, and parathyroid cells decrease the secretion of parathyroid hormone. Conversely, the activity of the CaSR decreases, and parathyroid hormone secretion increases as calcium levels decline.

• #1 Hypoparathyroidism – Parathyroid Gland Diseases – Endocrinology – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.10.1.

  Hypoparathyroidism is a condition associated with hypocalcemia and hyperphosphatemia in the presence of low or inappropriately normal parathyroid hormone (PTH) levels. […] It is associated with significant symptoms of hypocalcemia as well as long-term complications of inadequate PTH levels, hypocalcemia, and hyperphosphatemia. […] Autoimmune hypoparathyroidism is the most common cause of nonsurgical primary hypoparathyroidism. […] In isolated autoimmune hypoparathyroidism, activating antibodies directed to the calcium-sensing receptor (CaSR) cause decreased PTH secretion. […] Genetic causes can be divided into 2 main categories: syndromic and nonsyndromic. […] DiGeorge syndrome occurs due to a deletion at the site of chromosome 22q11.2, which leads to a developmental defect of the pharyngeal pouches and results in hypoparathyroidism in addition to several immunologic, cardiac, renal, and developmental anomalies.

• #1 Management of hypoparathyroidism: a Position Statement of the Expert Group of the Polish Society of Endocrinology | Misiorowski | Endokrynologia Polska

  https://journals.viamedica.pl/endokrynologia_polska/article/view/96950

  Parathyroid hormone is the main regulator of calcium and phosphate homeostasis. It shows direct activity in the bones and kidneys, while in the gastrointestinal tract, it acts indirectly by regulating renal 1a-hydroxylase activity and calcitriol synthesis. An inverse steep sigmoidal relationship between serum calcium concentrations (Ca++) and PTH secretion is mediated by the CaSR located on the surface of parathyroid cells. In cases of insufficient PTH production, there is a decrease in the tubular maximum for calcium reabsorption with a concomitant increase in tubular maximum phosphate reabsorption. These 2 pathophysiological processes are, at least in part, responsible for the characteristic biochemical abnormalities of HypoPT: hypocalcemia and hyperphosphatemia. Neuromuscular irritability, one of the cardinal clinical features of HypoPT, is caused by hypocalcemia. Ectopic deposition of insoluble calcium phosphate complexes in soft tissues is primarily due to hyperphosphatemia and increased levels of the calcium-phosphate product. Ectopic calcification can also occur in chronic hyperphosphatemia, even if the levels of the calcium-phosphate product are not elevated.

• #1 Hypoparathyroidism: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/122207-overview

  Hypoparathyroidism is a condition of parathyroid hormone (PTH) deficiency. Primary hypoparathyroidism, the subject of this article, is a state of inadequate PTH activity; this syndrome results from iatrogenic causes or one of many rare diseases. In the absence of adequate PTH activity, the ionized calcium concentration in the extracellular fluid falls below the reference range. […] The intracellular mechanism(s) whereby activation of the extracellular calcium-sensing receptor leads to inhibition of PTH exocytosis is unknown. Because pertussis toxin blocks the inhibition of cyclic adenosine monophosphate (cAMP), but not PTH, in response to a high ECF ionized calcium concentration, cAMP is probably not an important second messenger for the extracellular calcium-sensing receptor. […] In the absence of PTH, bone resorption, phosphaturic effect, renal distal tubular calcium reabsorption, and 1,25-dihydroxy vitamin D-mediated dietary calcium absorption cannot occur. Therefore, the consequence of PTH deficiency is hypocalcemia.

• #1 The Pathophysiology of Hypoparathyroidism

  https://www.knowhypopara.com/understand-hypoparathyroidism/pathophysiology/

  Hypoparathyroidism Is Characterized by the Absence or Deficiency of Parathyroid Hormone […] The absence or deficiency of PTH results in: […] Inhibition of calcitriol (active vitamin D) synthesis in the kidneys […] Leading to the indirect effect of reduced calcium absorption in the intestines […] Disruption of calcium/phosphate balance […] Reduced physical functioning and well-being […] PTH deficiency disrupts: […] Physiological access to calcium reservoirs in the bone […] The regulation of osteoclast and osteoblast activity […] Bone remodeling, leading to hypermature bone that may be more prone to fractures

• #1 Etiology and Pathophysiology of Hypoparathyroidism: A Narrative Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10364481/

  The approach utilized a systematic review of the medical literature executed with specifically designed criteria that focused on the etiologies and pathogenesis of hypoparathyroidism. […] Nonsurgical etiologies account for a significant proportion of cases of hypoparathyroidism (~25%), and among them, genetic etiologies are key. […] Approximately 25% of adults with hypoparathyroidism have a developmental, genetic, autoimmune, metabolic, or environmental condition that impairs either the secretion or action of PTH or alters parathyroid gland mass. […] Autoimmune hypoparathyroidism can occur as an isolated endocrinopathy or as a part of the autoimmune polyglandular syndrome type I (APS-1), a genetic disorder caused by mutations in the autoimmune regulator (AIRE) gene. […] The genetic disorders that are associated with hypoparathyroidism are discussed more fully elsewhere. […] The mechanism underlying the profound increase in bone mass in hypoparathyroidism is not clearly understood. […] Many etiologies for hypoparathyroidism have been identified, but the pathogenesis is unexplained in a large number of patients.

• #1 SciELO Brazil – Hypoparathyroidism and pseudohypoparathyroidism: etiology, laboratory features and complications Hypoparathyroidism and pseudohypoparathyroidism: etiology, laboratory features and complications

  https://www.scielo.br/j/aem/a/kf9fRZjjYhpM7NjByF6VPrD/

  Recently, renal complications have been linked to HP. In fact, as the activity of PTH in the renal tubules favoring calcium reabsorption is not repaired, the supplemented calcium is rapidly excreted in the urine. Furthermore, the doses of calcium and vitamin D are usually very high and hypercalciuria is often seen in these patients. Chronic hypercalciuria may lead to nephrocalcinosis, nephrolithiasis, and renal failure. […] Kidney calcification and renal function impairment were present in a great number of patients; however, our patients did not have hypercalciuria and the calcium level was within the target range. Kidney calcification and renal function impairment were present in a great number of patients even though mean serum and urinary calcium levels were within the target range. However, higher levels of urinary calcium excretion were seen in patients with renal calcification, suggesting that a upper limit of 4.0 mg/kg/d of urinary calcium (normal range) might not be appropriate for HP patients. Indeed, lower levels of urinary calcium should be the goal for these patients in order to prevent renal complications.

• #1 Hypoparathyroidism: Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/22672-hypoparathyroidism

  Hypoparathyroidism is a rare, treatable condition that happens when you have low levels of parathyroid hormone in your blood, which causes you to have low levels of calcium (hypocalcemia) and high levels of phosphorous in your blood. […] Hypoparathyroidism can lead to electrolyte imbalance since it causes low levels of calcium and high levels of phosphorous in your blood. […] Causes of hypoparathyroidism include damage to your parathyroid glands, certain genetic conditions, certain autoimmune diseases, infiltrative disorders, and low levels of magnesium. […] Approximately 75% of hypoparathyroidism cases are from accidental damage to your parathyroid glands from neck or thyroid surgery. […] Genetic causes of hypoparathyroidism represent fewer than 10% of cases. […] A disease called type 1 autoimmune polyglandular syndrome causes your immune system to attack your parathyroid glands, which causes chronic hypoparathyroidism.

• #1 Hypoparathyroidism: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/000385.htm

  Hypoparathyroidism is a disorder in which the parathyroid glands in the neck do not produce enough parathyroid hormone (PTH). […] Hypoparathyroidism occurs when the glands produce too little PTH. The blood calcium level falls, and the phosphorus level rises. […] The most common cause of hypoparathyroidism is injury to the parathyroid glands during thyroid or neck surgery. […] Autoimmune attack on the parathyroid glands (common) […] DiGeorge syndrome is a disease in which hypoparathyroidism occurs because all the parathyroid glands are missing at birth. […] Familial hypoparathyroidism occurs with other endocrine diseases such as adrenal insufficiency in a syndrome called type I polyglandular autoimmune syndrome (PGA I).

• #1 The PGRIS and parathyroid splinting concepts for the analysis and prognosis of protracted hypoparathyroidism – Sitges-Serra – Gland Surgery

  https://gs.amegroups.org/article/view/16238/html

  Most patients with hypocalcemia after total thyroidectomy will recover the parathyroid function in a few weeks, but some 20-30% of them will still be in the need for replacement therapy one month after surgery and about 5-10% of those will develop permanent hypoparathyroidism. […] The number of parathyroid glands remaining in situ (PGRIS) is a key variable to understand the pathogenesis of protracted hypoparathyroidism and the chances for restoration of the parathyroid function. […] This we refer to as parathyroid splinting, a hypothesis holding that putting the injured parathyroid parenchyma at rest after thyroidectomy may improve long-term outcome of protracted hypoparathyroidism. […] Several demographic, disease-related and surgical variables have been implicated through different mechanisms in the pathogenesis of postoperative hypocalcemia.

• #1 Calcium-sensing receptor autoantibody-mediated hypoparathyroidism associated with immune checkpoint inhibitor therapy: diagnosis and long-term follow-up | Journal for ImmunoTherapy of Cancer

  https://jitc.bmj.com/content/8/1/e000687

  Hypoparathyroidism is exceedingly rare. […] The etiology of hypocalcemia is likely autoimmune hypoparathyroidism caused by the development of CaSR-activating antibodies that might prevent PTH release from the parathyroid. […] Autoimmune hypoparathyroidism can occur in isolation or as part of Autoimmune Polyglandular Syndrome Type 1 (APS1). […] The detection of CaSR-activating antibodies matching the patients clinical course further supports a diagnosis of autoimmune hypoparathyroidism caused by the development of CaSR antibodies that could inhibit PTH release from the parathyroid even at below optimum levels of blood calcium. […] In some cases, CaSR antibodies have been shown to modulate the receptors function such that its response to calcium is adversely affected. […] The underlying mechanism of ICI-related hypoparathyroidism likely involves the formation of CaSR-activating antibodies.

• #1

  https://omim.org/entry/146200

  In HEK293 cells transfected with C18R-mutant preproPTH cDNA, Datta et al. (2007) demonstrated that the expressed mutant hormone was trapped intracellularly, predominantly in the endoplasmic reticulum (ER), resulting in apoptosis. […] Datta et al. (2007) suggested that ER stress-induced cell death is the underlying mechanism for autosomal dominant hypoparathyroidism.

• #1 Hypoparathyroidism – Parathyroid Gland Diseases – Endocrinology – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.10.1.

  Autosomal dominant hypocalcemia (ADH) type 1 is a nonsyndromic cause that occurs due to an activating (gain of function) sequence variation of the CASR gene. […] This results in hypocalcemia due to decreased synthesis and secretion of PTH. […] Infiltrative causes include destruction of the parathyroid glands secondary to granulomatous infiltration (eg, Riedel thyroiditis, amyloidosis, sarcoidosis). […] Metastatic cancer cells infiltrate the parathyroid gland leading to hypoparathyroidism. […] Wilson disease causes hypoparathyroidism due to copper infiltration and destruction of parathyroid glands. […] Hemochromatosis is an inherited disorder resulting in increased iron deposition in various organs, including the parathyroid glands, which leads to parathyroid gland dysfunction. […] Functional hypoparathyroidism is caused by hypomagnesemia as well as hypermagnesemia, both of which impair parathyroid function.

• #1

  https://journals.lww.com/ipcr/fulltext/2021/01010/hypoparathyroidism_precipitated_by_mumps__an.11.aspx

  Hypoparathyroidism is a condition characterized by hypocalcemia and hyperphosphatemia due to insufficient secretion of parathyroid hormone (PTH). […] Hypoparathyroidism was suspected and confirmed by low PTH levels. […] Although viral infections have been described as triggers for other endocrinopathies, we could not find any association with hypoparathyroidism. […] Whether mumps infection had any role in the pathogenesis of the hypoparathyroidism or only unmasked an underlying endocrinopathy remains uncertain. […] The presumption that the hypoparathyroidism was due to mumps is by the exclusion of other causes. […] We were unable to find any previous reports of a temporal association between mumps and hypoparathyroidism. […] If more cases are identified, it could generate some worthwhile research questions to explore the relationship between mumps and hypoparathyroidism.

• #1 Inflammation-induced hypoparathyroidism triggered by combination immune checkpoint blockade for melanoma | Journal for ImmunoTherapy of Cancer

  https://jitc.bmj.com/content/7/1/52

  Background Treatment with a combination of PD-1 and CTLA-4 targeted checkpoint inhibition has improved outcome of melanoma patients and led to durable remissions but is also associated with significant toxicities. Endocrinopathies such as thyroiditis and hypophysitis are often seen, but other, rarer disturbances have also been described. Endocrinopathies affecting the parathyroid gland are rarely reported and no clear pathomechanism has been proposed. […] Our report demonstrates a rare endocrinopathy as a complication of combined PD-1 and CTLA-4 blockade. In addition, it provides evidence from the course of the disease that inflammation within the parathyroid gland is involved in the mechanism. […] Immune-mediated endocrinopathies are among the most common irAEs. The most frequently reported immune-mediated endocrinopathies are hypophysitis and thyroid dysfunction while type 1 diabetes mellitus and adrenal insufficiency are less commonly reported.

• #1 Hypoparathyroidism – Parathyroid Gland Diseases – Endocrinology – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.10.1.

  Maternal hyperparathyroidism can result in suppressed parathyroid function in infants exposed to hypercalcemia in utero. […] Idiopathic hypoparathyroidism is confirmed if the cause of hypoparathyroidism is not identified after laboratory, genetic, or clinical evaluation. […] Pseudohypoparathyroidism (PHP) is defined as target organ resistance to PTH. […] PHP is characterized by elevated PTH levels in association with low serum calcium and high phosphate levels. […] Secondary hypoparathyroidism is not a disease state but a physiologic response, where PTH levels are low in response to a primary process that has caused hypercalcemia, not hypocalcemia.

• #1 Pediatric Hypoparathyroidism: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/922204-overview

  PHP Ia is due to loss-of-function mutations of the subunit of the G proteincoupled calcium-sensing receptor (Gsa). […] PHP and PPHP are manifestations of imprinting of the stimulatory G protein defect located on chromosome arm 20q. […] PHP Ib arises from epigenetic defects in the imprinted gene GNAS, which encodes the alpha subunit of the stimulatory G protein and the NESP55 protein. […] PHP II: Patients with PHP II have normal physical appearance. There is no association with the AHO phenotype. The genetic basis of PHP II is unknown. The defect appears to lie downstream of the signal for cAMP generation because PTH causes an increase in urinary cAMP without the phosphaturia that normally accompanies PTH stimulation.

• #1 Management of hypoparathyroidism: a Position Statement of the Expert Group of the Polish Society of Endocrinology | Misiorowski | Endokrynologia Polska

  https://journals.viamedica.pl/endokrynologia_polska/article/view/96950

  The complete clinical picture of HypoPT (signs, symptoms, and complications) is a direct consequence of parathyroid gland damage or dysfunction and, in particular, of deficient PTH secretion or receptor resistance to PTH, resulting in the lack of PTH signaling in the classic target tissues (bone and kidney) as well as in other tissues demonstrating the expression of PTH receptors. Therefore, HypoPT is a disease caused by the lack of PTH secretion or PTH signaling. Over a person’s lifetime, the consequences of HypoPT can involve almost every organ in the body. In addition, the standard management of hypocalcemia, consisting of oral calcium agents and calcitriol or other active vitamin D analogues, can alleviate disease symptoms, while at the same time causing a number of side effects.

• #1 Hypoparathyroidism presenting with late onset seizures – a report of two cases from rural India

  https://www.oaepublish.com/articles/2347-8659.2017.65

  Acquired chronic hypoparathyroidism is generally the after effect of unintentional surgical removal of all the parathyroid glands. […] The essential capacity of PTH is to keep up the extracellular fluid (ECF) calcium concentration within a normal narrow range. […] Hypocalcemia produces hyperexcitability of nerve fibers with spontaneous and repetitive discharges. […] Seizures are a frequent complication: they have been reported in 20%-25% of patients with acute hypocalcemia and in 30%-70% of patients with idiopathic hypoparathyroidism. […] Seizures are thought to occur due to hypocalcemia and intracranial calcification that occur in vascular and perivascular locations. […] Eaton et al. in 1939 first described basal ganglia calcification (BGC) in association with chronic hypoparathyroidism. Pathogenesis is obscure, but its occurrence with hypocalcemia signifies an important role of increased calcium-phosphorus complex formation.

• #1 Hypoparathyroidism presenting with late onset seizures – a report of two cases from rural India

  https://www.oaepublish.com/articles/2347-8659.2017.65

  Hypoparathyroidism leading to hypocalcaemia is an important treatable cause of recurrent seizures. Neurological manifestations due to hypoparathyroidism include: seizures, paresthesia, depression, psychosis, extra pyramidal symptoms, and features of raised intracranial pressure. […] Primary hypoparathyroidism presenting for the first time as seizures in the elderly is quite rare. […] Hypoparathyroidism occurs when too little parathyroid hormone (PTH) is released from the parathyroid glands, or the released PTH does not work properly. Common clinical manifestations of hypoparathyroidism include tingling and numbness, carpopedal spasm, neurocognitive dysfunction and seizures. […] Hypoparathyroidism can be caused by congenital disorders (like Di George syndrome, mitochondrial cytopathies), receptor insensitivity (pseudohypoparathyroidism type Iac, II), surgery, autoimmune disorders (familial autoimmune polyglandular syndrome type I), or hemochromatosis, or can be idiopathic.

• #1 Basal ganglia calcification in idiopathic hypoparathyroidism | British Columbia Medical Journal

  https://bcmj.org/articles/basal-ganglia-calcification-idiopathic-hypoparathyroidism

  Hypoparathyroidism refers to a group of disorders in which extracellular calcium levels cannot be maintained within the normal range due to relative or absolute deficiency of parathyroid hormone. […] The most common causes of pathological BGC are hypoparathyroidism and pseudo-hypoparathyroidism. […] Pathogenesis is unknown, but its occurrence with hypocalcemia suggests that increased calcium-phosphorus complex formation plays a role. […] Basal ganglia calcification in idiopathic hypoparathyroidism is a progressive disorder and has been observed to worsen despite maintenance of normal calcium levels. […] These findings suggest that early diagnosis and strict control of phosphorus is another crucial component in treating and preventing progression of BGC. […] Despite some uncertainty about the exact pathogenesis of BGC, treatment is known to prevent progression.

• #1

  https://link.springer.com/article/10.1007/s40618-022-01822-6

  A potential direct role of PTH on the central nervous system and brain has been proposed as possibly pivotal in the etiopathogenesis of neurocognitive symptoms in patients with HypoPT. […] Ultimately, the emerging role of PTH in the brain has pushed research to deeply investigate the mechanisms of neuropsychological involvement during Hypo-PT and sophisticated approaches using magnetic resonance imaging (MRI) in clinical trials which are still ongoing. […] In conclusion, we show that patients with chronic PS-HypoPT treated with conventional therapy do not show a severe cognitive impairment, which is frequent in patients with idiopathic HypoPT. Nonetheless, some cognitive functions such as visuo-spatial attention, executive function and semantic memory appear to be modulated by Alb-Ca and endangered by its low levels.

• #1 How Hypoparathyroidism May Affect Your HeartEnvelope icon

  https://hypoparathyroidismnews.com/health-insights/how-hypoparathyroidism-may-affect-your-heart/

  Hypoparathyroidism is characterized by low levels of calcium. Low calcium levels can lead to a number of symptoms and may have a negative effect on the heart, among other organs. […] Hypoparathyroidism is the result of the body producing too little parathyroid hormone (PTH). PTH helps to regulate the levels of calcium and phosphate in the body. The four parathyroid glands in the neck — two on each side — are responsible for producing PTH. […] Hypoparathyroidism has several causes, but damage or accidental removal of the parathyroid glands during neck surgeries is the most common. Other causes include autoimmune diseases, radiation treatment, low levels of magnesium, or genetic mutations. […] Patients with hypoparathyroidism may have a higher risk of heart problems. Medical literature contains examples of patients experiencing a number of complications related to hypoparathyroidism, including heart arrhythmias (irregular heartbeats) and dilated cardiomyopathy (a condition in which the part of the heart that pumps blood to the rest of the body becomes stretched, thin, and weak). Both of these issues can make it harder for the heart to pump blood to the rest of the body.

• #1 How Hypoparathyroidism May Affect Your HeartEnvelope icon

  https://hypoparathyroidismnews.com/health-insights/how-hypoparathyroidism-may-affect-your-heart/

  The exact mechanism of how hypoparathyroidism can lead to heart problems is not clear. Researchers think that arrhythmias may be due to hypocalcemia (low levels of calcium). Calcium is an important molecule for the function of the nervous system and the ability of heart muscles to contract. Low levels of calcium can lead to trouble with signals from the autonomic nervous system to the heart. It also may cause changes in the flow of signals between heart cells, leading to an irregular rhythm.

• #1 Increased arterial stiffness in normotensive individuals with hypoparathyroidism | Scientific Reports

  https://www.nature.com/articles/s41598-025-92708-z

  The aim of the present research was to evaluate whether central hemodynamic parameters, particularly AS, are altered in post-surgical hypoparathyroidism patients and investigate any association between calcium metabolism parameters and AS. […] The present study evaluated the AS by PWV in patients with post-surgical hypoparathyroidism. […] Clinical, BP and laboratorial parameters investigated in this study demonstrated that hypoparathyroidism is associated with higher BP and AS, thereby contributing to increased cardiovascular risk. […] According to multivariate linear regression analysis, ionized calcium, phosphorus, and the Ca x P product are independent predictors for PWV. […] Although the present study demonstrated that calcium, phosphorus and the Ca x P product were adequate in serum, these parameters were correlated to AS.

• #1 Hypoparathyroidism – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441899/

  Parathyroid hormone activates the PTH receptor, another G-protein coupled receptor, increasing the resorption of calcium and phosphorus from bone, enhancing the distal tubular reabsorption of calcium, and decreasing the renal tubular reabsorption of phosphorus. […] Consequently, PTH deficiency results in hypocalcemia and hyperphosphatemia, while alkaline phosphatase, a marker of bone formation, is normal. […] Additionally, magnesium depletion can cause hypocalcemia by inducing a state of parathyroid hormone resistance. When patients are severely depleted, PTH secretion is also decreased.

• #1 Pediatric Hypoparathyroidism: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/922204-overview

  Hypoparathyroidism results from defective synthesis or secretion of parathyroid hormone (PTH), end-organ resistance, or inappropriate regulations that result from the activated or antibody-stimulated calcium-sensing receptor (CaSR). […] The net effects of PTH activity are an increase in serum calcium and a decrease in serum phosphate. PTH acts directly on bone to stimulate bone resorption and cause calcium and phosphate release. […] Hypoparathyroidism results in loss of both the direct and indirect effects of PTH on bone, the kidney, and the gut. Calcium and phosphate release from bone is impaired, calcium absorption from the gut is limited, calciuria develops despite hypocalcemia, and retention of phosphate from the urine causes increased plasma phosphate levels. […] Defects in PTH action occur in PHP. The hallmark of PHP is PTH resistance.

• #1 Hypoparathyroidism in Dogs – Musculoskeletal System – Merck Veterinary Manual

  https://www.merckvetmanual.com/musculoskeletal-system/dystrophies-associated-with-calcium-phosphorus-and-vitamin-d/hypoparathyroidism-in-dogs

  The functional disturbances and clinical manifestations of hypoparathyroidism primarily are the result of increased neuromuscular excitability and tetany. […] Blood phosphorus levels are increased substantially, owing to increased renal tubular reabsorption. […] Hyperphosphatemia triggers an upregulation of the synthesis of fibroblast growth factor 23 in bone, which hampers the hydroxylation of vitamin D3 in the kidney to its active form. […] This further impairs the counter-regulatory response to hypocalcemia.

• #1 Non-nuclear cataracts in hypoparathyroidism are associated with biochemical control of the disease | ECE2021 | European Congress of Endocrinology 2021 | Endocrine Abstracts

  https://www.endocrine-abstracts.org/ea/0073/ea0073aep84

  A high calcium-phosphate product is thought to increase the risk of soft tissue calcification in hypoparathyroidism, including cataracts. […] However, the mechanism of cataract formation is still not well understood. […] Peripheral damage to the lens is characteristic of hypoparathyroidism and may be correlated with hypocalcemia and hyperphosphatemia. Control of these biochemical abnormalities may reduce the risk of this complication.

• #1

  https://link.springer.com/article/10.1007/s40618-020-01355-w

  Hypoparathyroidism and pseudohypoparathyroidism are rare disorders of mineral metabolism which may be associated with soft tissue calcification in the basal ganglia in the brain, and occasionally the skin and other tissues. […] The reasons why the basal ganglia are a common site of soft tissue calcification in these rare disorders has been a matter of investigation for many years. […] There is evidence that the absence of parathyroid hormone in hypoparathyroidism may play a direct role, but this is clearly not the case in pseudohypoparathyroidism, which is associated with increased parathyroid hormone levels. […] Maintaining the calcium/phosphorus ratio as close to normal as possible, and maintaining normal serum phosphate levels, may help mitigate the progression of BGC. […] This review will focus on the pathophysiology of BGC in hypoparathyroidism and pseudohypoparathyroidism, and review the proposed pathophysiologic mechanisms, as well as the clinical implications of BGC on patient quality of life. […] Expression of osteogenic molecules in the caudate nucleus and gray matter and their potential relevance for basal ganglia calcification in hypoparathyroidism.

• #1 Treatment of Hypoparathyroidism by Re-Establishing the Effects of Parathyroid Hormone

  https://www.e-enm.org/journal/view.php?doi=10.3803/EnM.2024.1916

  Hypoparathyroidism (HypoPT) is a disease involving hypocalcemia due to insufficient levels of parathyroid hormone (PTH). […] Different mechanisms may be responsible for non-surgical HypoPT with impaired synthesis or secretion of PTH, including genetic or autoimmune causes. […] PTH normally affects the renal handling of calcium and phosphate. […] Accordingly, in addition to hypocalcemia, HypoPT is often associated with both hypercalciuria and high plasma phosphate levels with a high CaxP product. […] Despite achieving normocalcemia in response to conventional therapy, patients often experience unpredicted fluctuations in plasma calcium levels causing hypo- or hypercalcemic symptoms. […] In recent years, several studies have reported on the treatment of HypoPT with replacement therapy with the missing hormone (i.e., PTH) or drugs that act in a similar manner.

• #1 SciELO Brazil – Treatment options in hypoparathyroidism Treatment options in hypoparathyroidism

  https://www.scielo.br/j/aem/a/ZcTLsZtMmL6qJkmrh4q6X9b/?lang=en

  Hypoparathyroidism is a rare endocrine disease characterized by hypocalcemia associated with hyperphosphatemia and concomitant absent or inappropriately low levels of parathyroid hormone (PTH) (1). […] When the parathyroid glands are compromised, PTH production and release are jeopardized, failing to rise in response to hypocalcemia. In this setting, little or no mobilization of the skeleton or increase in renal resorption occurs to increase calcium levels along with inadequate conversion of vitamin D to its active form, 1,25-dihydroxyvitamin D, which in turn increases the gut absorption of calcium (1). […] Replacement with the missing hormone is still not the first choice treatment for hypoparathyroidism. […] The first studies with PTH analogs were conducted by Winer and cols., who treated adults with PTH (134), initially with a single daily dose (24) but switched to two daily doses due to its short half-life (25,26).

• #1 A translational approach to investigate the mechanism whereby eneboparatide induces prolonged calcium normalization in patients with chronic hypoparathyroidism | ECE2024 | 26th European Congress of Endocrinology | Endocrine Abstracts

  https://www.endocrine-abstracts.org/ea/0099/ea0099oc2.3

  A translational approach to investigate the mechanism whereby eneboparatide induces prolonged calcium normalization in patients with chronic hypoparathyroidism. […] Maintaining normal serum and urinary calcium in patients with chronic hypoparathyroidism (cHP) remains a therapeutic challenge. […] Eneboparatide is a hybrid analog of PTH and PTH-related peptide specifically designed to induce prolonged activation of the PTH1R. […] To gain deeper insight into the mechanism whereby eneboparatide provides sustained calcium normalization, we analyzed tissue distribution and retention of eneboparatide in comparison to natural PTH(1-34) following subcutaneous injection in rats. […] These results demonstrated a preferential retention of eneboparatide in the renal cortex, where the PTH1R regulates calcium reabsorption.

• #1 A translational approach to investigate the mechanism whereby eneboparatide induces prolonged calcium normalization in patients with chronic hypoparathyroidism | ECE2024 | 26th European Congress of Endocrinology | Endocrine Abstracts

  https://www.endocrine-abstracts.org/ea/0099/ea0099oc2.3

  We next assessed whether the eneboparatide tissue retention observed in vivo was due to prolonged binding to the PTH1R. […] Our translational approach demonstrates the potential therapeutic advantage of eneboparatide over PTH(1-34) due to its ability to be retained in renal cortex, to induce a prolonged activation of the PTH1R and to maintain normal serum and urinary calcium over 24 hours in cHP patients.

• #1 Treatment of Hypoparathyroidism by Re-Establishing the Effects of Parathyroid Hormone

  https://www.e-enm.org/journal/view.php?doi=10.3803/EnM.2024.1916

  Encaleret is an oral CaSR antagonist (calcilytic), thereby addressing the underlying molecular pathophysiological mechanism. […] Despite normalizing plasma calcium levels, thereby alleviating severe symptoms of hypocalcemia, conventional treatment of HypoPT with active vitamin D and calcium supplements is associated with unpredictable fluctuations in plasma calcium levels, hypercalciuria, and several complications, including an increased risk of impaired kidney function and impaired QoL. […] Substitution with the missing hormone using rhPTH(1-84) or PTH(1-34) has been shown to reduce the need for conventional therapy; however, due to the short duration of action, replacement therapy with these analogues is not ideal. […] Treatment with eneboparatide and encaleret also seems to cause long-acting effects on the calcium-PTH axis, and phase 3 clinical trials are currently ongoing aiming to demonstrate a normalization of calcium homeostasis in response to treatment of patients with chronic HypoPT.

• #1 Potential of Calcilytics as a Novel Treatment for Post-Surgical Hypoparathyroidism

  https://e-enm.org/journal/view.php?number=2498

  Post-surgical hypoparathyroidism is a well-recognized complication after thyroid surgery or operations in other parts of the neck. It results from inadvertent or unavoidable damage to the parathyroid glands and/or their blood supply during surgery. Biochemically, hypoparathyroidism is characterized by hypocalcemia, hyperphosphatemia, and increased fractional excretion of calcium in the urine, and the extent of these biochemical derangements can vary depending on the degree of damage to the parathyroid glands. […] A new drug being investigated with a different mechanism from PTH analogues is encaleret, a calcium-sensing receptor (CaSR) antagonist or calcilytic that binds to CaSR on parathyroid cells and antagonizes the inhibitory signal of PTH secretion, consequently leading to the hypersecretion of PTH.

• #1 The PGRIS and parathyroid splinting concepts for the analysis and prognosis of protracted hypoparathyroidism – Sitges-Serra – Gland Surgery

  https://gs.amegroups.org/article/view/16238/html

  Here is where the number of parathyroid glands remaining in situ (PGRIS) concept has been particularly helpful in providing a tool to analyze the failure to recover early from postoperative hypocalcemia. […] It makes sense that autotransplantation and inadvertent parathyroid gland excision have been shown to be associated with postoperative hypocalcemia since they both reduce the amount of functioning parathyroid parenchyma left after thyroidectomy. […] PGRIS is easily calculated by subtracting the number of parathyroid glands inadvertently excised and identified by the pathologist or autografted, from 4, the number of whole parathyroid glands found in normal anatomy. […] The prevalence of postoperative hypocalcemia, and of protracted and permanent hypoparathyroidism was inversely related to the PGRIS group.

• #1 Potential of Calcilytics as a Novel Treatment for Post-Surgical Hypoparathyroidism

  https://e-enm.org/journal/view.php?number=2498

  The mechanism through which AXT914 enhanced angiogenesis is unclear. A previous ex vivo study showed that PTH induced angiogenesis in isolated rat microvessels embedded in a three-dimensional collagen I matrix, for which VEGF expression was essential. […] In conclusion, our findings suggest that calcilytics have potential as a new therapeutic agent to restore damaged or autotransplanted parathyroid tissue, while avoiding adverse effects such as renal complications and ectopic calcification in postsurgical hypoparathyroidism.

• #1 Inflammation-induced hypoparathyroidism triggered by combination immune checkpoint blockade for melanoma | Journal for ImmunoTherapy of Cancer

  https://jitc.bmj.com/content/7/1/52

  Autoimmune hypoparathyroidism can be caused by either immune-mediated destruction or by hyperactivation of the CaSR by activating autoantibodies. Interestingly, we find that the hypoparathyroidism in the described patient was dependent on immune-suppressive medication and therefore was rather inflammation-mediated. Since we could not detect significant titers of anti-CaSR antibodies in our patient, it seems the pathomechanism is probably distinct from the one seen in sporadic hypoparathyroidism. […] This case describes a rare immune-related endocrinopathy in a patient treated with combination immune checkpoint blockade for melanoma. Therefore, physicians caring for cancer patients treated with ICI should be aware of such irAEs. We also demonstrate that this patient has an inflammation-driven and not an autoantibody-mediated irAE. Our case report therefore also provides a new insight into the pathomechanism of this rare side effect of ICI treatment.

• #1 Idiopathic Hypoparathyroidism in a Dog in: Journal of the American Veterinary Medical Association Volume 168 Issue 9 (1976)

  https://avmajournals.avma.org/view/journals/javma/168/9/javma.1976.168.09.858.xml

  Idiopathic hypoparathyroidism in a 3-year-old dog was manifested clinically as periodic episodes of depression, vomiting, and tetanic convulsions. […] The pathologic features were similar to those reported in dogs in which hypoparathyroidism was induced by injection of homologous parathyroid tissue, thus suggesting an autoimmune pathogenesis.

• #2 Hypoparathyroidism – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hypoparathyroidism/symptoms-causes/syc-20355375

  Hypoparathyroidism is an uncommon condition in which the body produces abnormally low levels of parathyroid hormone (PTH). parathyroid hormone (PTH) is key to regulating and maintaining a balance of two minerals in the body calcium and phosphorus. […] The low production of PTH in hypoparathyroidism leads to abnormally low calcium levels in the blood and an increase of phosphorus in the blood. […] Hypoparathyroidism occurs when the parathyroid glands don’t produce enough parathyroid hormone. There are four small parathyroid glands in the neck behind the thyroid gland. […] Parathyroid hormone controls the levels of calcium and phosphorus, so too little parathyroid hormone causes abnormal levels of: […] Causes of hypoparathyroidism can include: […] Autoimmune disease. In some cases, the immune system attacks parathyroid tissues as if they were foreign bodies. In the process, the parathyroid glands stop producing their hormone.

• #2 Hypoparathyroidism: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/122207-overview

  Hypoparathyroidism is a condition of parathyroid hormone (PTH) deficiency. Primary hypoparathyroidism, the subject of this article, is a state of inadequate PTH activity; this syndrome results from iatrogenic causes or one of many rare diseases. In the absence of adequate PTH activity, the ionized calcium concentration in the extracellular fluid falls below the reference range. […] The intracellular mechanism(s) whereby activation of the extracellular calcium-sensing receptor leads to inhibition of PTH exocytosis is unknown. Because pertussis toxin blocks the inhibition of cyclic adenosine monophosphate (cAMP), but not PTH, in response to a high ECF ionized calcium concentration, cAMP is probably not an important second messenger for the extracellular calcium-sensing receptor. […] In the absence of PTH, bone resorption, phosphaturic effect, renal distal tubular calcium reabsorption, and 1,25-dihydroxy vitamin D-mediated dietary calcium absorption cannot occur. Therefore, the consequence of PTH deficiency is hypocalcemia.

• #2 Hypoparathyroidism – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441899/

  Parathyroid hormone activates the PTH receptor, another G-protein coupled receptor, increasing the resorption of calcium and phosphorus from bone, enhancing the distal tubular reabsorption of calcium, and decreasing the renal tubular reabsorption of phosphorus. […] Consequently, PTH deficiency results in hypocalcemia and hyperphosphatemia, while alkaline phosphatase, a marker of bone formation, is normal. […] Additionally, magnesium depletion can cause hypocalcemia by inducing a state of parathyroid hormone resistance. When patients are severely depleted, PTH secretion is also decreased.

• #2 Management of hypoparathyroidism: a Position Statement of the Expert Group of the Polish Society of Endocrinology | Misiorowski | Endokrynologia Polska

  https://journals.viamedica.pl/endokrynologia_polska/article/view/96950

  Parathyroid hormone is the main regulator of calcium and phosphate homeostasis. It shows direct activity in the bones and kidneys, while in the gastrointestinal tract, it acts indirectly by regulating renal 1a-hydroxylase activity and calcitriol synthesis. An inverse steep sigmoidal relationship between serum calcium concentrations (Ca++) and PTH secretion is mediated by the CaSR located on the surface of parathyroid cells. In cases of insufficient PTH production, there is a decrease in the tubular maximum for calcium reabsorption with a concomitant increase in tubular maximum phosphate reabsorption. These 2 pathophysiological processes are, at least in part, responsible for the characteristic biochemical abnormalities of HypoPT: hypocalcemia and hyperphosphatemia. Neuromuscular irritability, one of the cardinal clinical features of HypoPT, is caused by hypocalcemia. Ectopic deposition of insoluble calcium phosphate complexes in soft tissues is primarily due to hyperphosphatemia and increased levels of the calcium-phosphate product. Ectopic calcification can also occur in chronic hyperphosphatemia, even if the levels of the calcium-phosphate product are not elevated.

• #2 Hypoparathyroidism pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Hypoparathyroidism_pathophysiology

  Hypoparathyroidism is a decrease in serum parathyroid hormone. Normally, parathyroid hormone increases serum calcium and magnesium concentration, and decreases serum phosphate concentration. Secretion of parathyroid hormone from parathyroid gland is stimulated by low serum calcium. Parathyroid glands have calcium-sensing receptors responsible for sensing extracellular ionized calcium. Calcium and magnesium provides a negative feedback for secretion of parathyroid hormone. Deficiency of parathyroid hormone causes body to decrease reabsorption of calcium from bone, excretion of phosphate, reabsorbtion of calcium from distal tubules, and vitamin D mediated absorption of calcium from intestine leading to hypocalcemia. Many genetic conditions are associated with hypoparathyroidism. Hypoparathyroidism associated with genetic defects may be either autoimmune hypoparathyroidism, isolated hypoparathyroidism, associated with congenital multisystem syndromes, or a part of metabolic disorders.

• #2 The Pathophysiology of Hypoparathyroidism

  https://www.knowhypopara.com/understand-hypoparathyroidism/pathophysiology/

  Hypoparathyroidism Is Characterized by the Absence or Deficiency of Parathyroid Hormone […] The absence or deficiency of PTH results in: […] Inhibition of calcitriol (active vitamin D) synthesis in the kidneys […] Leading to the indirect effect of reduced calcium absorption in the intestines […] Disruption of calcium/phosphate balance […] Reduced physical functioning and well-being […] PTH deficiency disrupts: […] Physiological access to calcium reservoirs in the bone […] The regulation of osteoclast and osteoblast activity […] Bone remodeling, leading to hypermature bone that may be more prone to fractures

• #2 Increased arterial stiffness in normotensive individuals with hypoparathyroidism | Scientific Reports

  https://www.nature.com/articles/s41598-025-92708-z

  Hypoparathyroidism is the inability of parathyroid hormone (PTH) to maintain calcium homeostasis. […] The effects of PTH on calcium and phosphorus levels have been described in respect to the cardiovascular system. PTH receptors in endothelial and myocardial cells and direct hypertrophic effects of PTH on myocardial cells have been reported. […] Although the mechanism is uncertain, hypocalcemia is believed to reduce myocardial contractility; QT prolongation and arrythmias may occur due to hypocalcemia. […] Moreover, persistent hyperphosphatemia has been associated to vascular calcification in patients with chronic kidney disease (CKD). […] As hyperphosphatemia is a characteristic of hypoparathyroidism, increased cardiovascular risk has been described in patients with this metabolic disorder.

• #2 Management of hypoparathyroidism: a Position Statement of the Expert Group of the Polish Society of Endocrinology | Misiorowski | Endokrynologia Polska

  https://journals.viamedica.pl/endokrynologia_polska/article/view/96950

  The complete clinical picture of HypoPT (signs, symptoms, and complications) is a direct consequence of parathyroid gland damage or dysfunction and, in particular, of deficient PTH secretion or receptor resistance to PTH, resulting in the lack of PTH signaling in the classic target tissues (bone and kidney) as well as in other tissues demonstrating the expression of PTH receptors. Therefore, HypoPT is a disease caused by the lack of PTH secretion or PTH signaling. Over a person’s lifetime, the consequences of HypoPT can involve almost every organ in the body. In addition, the standard management of hypocalcemia, consisting of oral calcium agents and calcitriol or other active vitamin D analogues, can alleviate disease symptoms, while at the same time causing a number of side effects.

• #2 SciELO Brazil – Treatment options in hypoparathyroidism Treatment options in hypoparathyroidism

  https://www.scielo.br/j/aem/a/ZcTLsZtMmL6qJkmrh4q6X9b/?lang=en

  A phase III, open-label, non-comparative study showed that teriparatide 20 g once daily was insufficient to discontinue calcium and calcitriol supplements to maintain normal calcemia. […] The use of PTH (134) seems to stimulate bone turnover, but reduced BMD of the distal radius has been reported (29), and no long-term safety data are available. […] In January 2015, the FDA approved PTH (1-84) for the treatment of hypoparathyroidism in patients with inadequate control with conventional treatment. […] The use of PTH analogs in the treatment of hypoparathyroidism is promising, but it is a high-cost injectable therapy that is currently indicated for patients in special situations, such as those using high doses of calcium and vitamin D without proper control, with poor adherence, or with the presence of gastrointestinal disorder with malabsorption.

• #2 SciELO Brazil – Hypoparathyroidism and pseudohypoparathyroidism: etiology, laboratory features and complications Hypoparathyroidism and pseudohypoparathyroidism: etiology, laboratory features and complications

  https://www.scielo.br/j/aem/a/kf9fRZjjYhpM7NjByF6VPrD/

  Recently, renal complications have been linked to HP. In fact, as the activity of PTH in the renal tubules favoring calcium reabsorption is not repaired, the supplemented calcium is rapidly excreted in the urine. Furthermore, the doses of calcium and vitamin D are usually very high and hypercalciuria is often seen in these patients. Chronic hypercalciuria may lead to nephrocalcinosis, nephrolithiasis, and renal failure. […] Kidney calcification and renal function impairment were present in a great number of patients; however, our patients did not have hypercalciuria and the calcium level was within the target range. Kidney calcification and renal function impairment were present in a great number of patients even though mean serum and urinary calcium levels were within the target range. However, higher levels of urinary calcium excretion were seen in patients with renal calcification, suggesting that a upper limit of 4.0 mg/kg/d of urinary calcium (normal range) might not be appropriate for HP patients. Indeed, lower levels of urinary calcium should be the goal for these patients in order to prevent renal complications.

• #2 Treatment of Hypoparathyroidism by Re-Establishing the Effects of Parathyroid Hormone

  https://www.e-enm.org/journal/view.php?doi=10.3803/EnM.2024.1916

  Encaleret is an oral CaSR antagonist (calcilytic), thereby addressing the underlying molecular pathophysiological mechanism. […] Despite normalizing plasma calcium levels, thereby alleviating severe symptoms of hypocalcemia, conventional treatment of HypoPT with active vitamin D and calcium supplements is associated with unpredictable fluctuations in plasma calcium levels, hypercalciuria, and several complications, including an increased risk of impaired kidney function and impaired QoL. […] Substitution with the missing hormone using rhPTH(1-84) or PTH(1-34) has been shown to reduce the need for conventional therapy; however, due to the short duration of action, replacement therapy with these analogues is not ideal. […] Treatment with eneboparatide and encaleret also seems to cause long-acting effects on the calcium-PTH axis, and phase 3 clinical trials are currently ongoing aiming to demonstrate a normalization of calcium homeostasis in response to treatment of patients with chronic HypoPT.

• #2 Hypoparathyroidism: Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/22672-hypoparathyroidism

  Hypoparathyroidism is a rare, treatable condition that happens when you have low levels of parathyroid hormone in your blood, which causes you to have low levels of calcium (hypocalcemia) and high levels of phosphorous in your blood. […] Hypoparathyroidism can lead to electrolyte imbalance since it causes low levels of calcium and high levels of phosphorous in your blood. […] Causes of hypoparathyroidism include damage to your parathyroid glands, certain genetic conditions, certain autoimmune diseases, infiltrative disorders, and low levels of magnesium. […] Approximately 75% of hypoparathyroidism cases are from accidental damage to your parathyroid glands from neck or thyroid surgery. […] Genetic causes of hypoparathyroidism represent fewer than 10% of cases. […] A disease called type 1 autoimmune polyglandular syndrome causes your immune system to attack your parathyroid glands, which causes chronic hypoparathyroidism.

• #2 A registry for patients with chronic hypoparathyroidism in Russian adults in: Endocrine Connections Volume 9 Issue 7 (2020)

  https://ec.bioscientifica.com/view/journals/ec/9/7/EC-20-0219.xml

  Hypoparathyroidism and pseudohypoparathyroidism are rare endocrine disorders, characterized by low serum calcium due to inappropriate parathyroid hormone (PTH) levels or resistance to its action. […] The most frequent cause of hypoparathyroidism was neck surgery (82.5%, mostly females), followed by idiopathic hypoparathyroidism (10%), syndromic forms of genetic hypoparathyroidism (4.5%) and forms of defective PTH action (3%). […] Consequently, substitution treatment with parathyroid hormone should be available in certain cases of hypoparathyroidism. […] The most common cause is post-surgical parathyroid damage which causes chronic hypoparathyroidism when PTH is consistently inappropriately low 6 months after surgery. […] However, due to the absence of a standard definition of hypocalcemia, the incidence of postsurgical hypoparathyroidism varies 0-20.2%.

• #2 Postsurgical Hypoparathyroidism: A Systematic Review | In Vivo

  https://iv.iiarjournals.org/content/30/3/171

  The extent of thyroidectomy has a significant impact on the occurrence of postoperative PHypo. Near total vs. total thyroidectomy has an advantage to avoid postoperative PHypo, especially in benign thyroid diseases. […] The presence of parathyroid gland in the histopathologic specimen (i.e., unintended removal of parathyroid gland) and the surgeon’s experience were recognized as important risk factors for permanent PHypo. […] The hungry bone syndrome is another cause of postoperative hypocalcaemia and can be seen after successful parathyroidectomy in patients with severe hyperparathyroid bone disease preoperatively or in cases of severe hyperthyroidism. […] This systematic review summarizes our current state of knowledge on postsurgical PHypo, a major disorder of parathyroid function, and its treatment modalities. Further research should be directed on the risk factors and the pathways of the pathophysiological mechanisms that may provide additional knowledge on prevention, etiology, molecular pathogenesis and other therapeutic approaches.

• #2 The PGRIS and parathyroid splinting concepts for the analysis and prognosis of protracted hypoparathyroidism – Sitges-Serra – Gland Surgery

  https://gs.amegroups.org/article/view/16238/html

  Here is where the number of parathyroid glands remaining in situ (PGRIS) concept has been particularly helpful in providing a tool to analyze the failure to recover early from postoperative hypocalcemia. […] It makes sense that autotransplantation and inadvertent parathyroid gland excision have been shown to be associated with postoperative hypocalcemia since they both reduce the amount of functioning parathyroid parenchyma left after thyroidectomy. […] PGRIS is easily calculated by subtracting the number of parathyroid glands inadvertently excised and identified by the pathologist or autografted, from 4, the number of whole parathyroid glands found in normal anatomy. […] The prevalence of postoperative hypocalcemia, and of protracted and permanent hypoparathyroidism was inversely related to the PGRIS group.

• #2 Hypoparathyroidism – Parathyroid Gland Diseases – Endocrinology – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.10.1.

  Hypoparathyroidism is a condition associated with hypocalcemia and hyperphosphatemia in the presence of low or inappropriately normal parathyroid hormone (PTH) levels. […] It is associated with significant symptoms of hypocalcemia as well as long-term complications of inadequate PTH levels, hypocalcemia, and hyperphosphatemia. […] Autoimmune hypoparathyroidism is the most common cause of nonsurgical primary hypoparathyroidism. […] In isolated autoimmune hypoparathyroidism, activating antibodies directed to the calcium-sensing receptor (CaSR) cause decreased PTH secretion. […] Genetic causes can be divided into 2 main categories: syndromic and nonsyndromic. […] DiGeorge syndrome occurs due to a deletion at the site of chromosome 22q11.2, which leads to a developmental defect of the pharyngeal pouches and results in hypoparathyroidism in addition to several immunologic, cardiac, renal, and developmental anomalies.

• #2 Calcium-sensing receptor autoantibody-mediated hypoparathyroidism associated with immune checkpoint inhibitor therapy: diagnosis and long-term follow-up | Journal for ImmunoTherapy of Cancer

  https://jitc.bmj.com/content/8/1/e000687

  Hypoparathyroidism is exceedingly rare. […] The etiology of hypocalcemia is likely autoimmune hypoparathyroidism caused by the development of CaSR-activating antibodies that might prevent PTH release from the parathyroid. […] Autoimmune hypoparathyroidism can occur in isolation or as part of Autoimmune Polyglandular Syndrome Type 1 (APS1). […] The detection of CaSR-activating antibodies matching the patients clinical course further supports a diagnosis of autoimmune hypoparathyroidism caused by the development of CaSR antibodies that could inhibit PTH release from the parathyroid even at below optimum levels of blood calcium. […] In some cases, CaSR antibodies have been shown to modulate the receptors function such that its response to calcium is adversely affected. […] The underlying mechanism of ICI-related hypoparathyroidism likely involves the formation of CaSR-activating antibodies.

• #2 Hypoparathyroidism – Parathyroid Gland Diseases – Endocrinology – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.10.1.

  Autosomal dominant hypocalcemia (ADH) type 1 is a nonsyndromic cause that occurs due to an activating (gain of function) sequence variation of the CASR gene. […] This results in hypocalcemia due to decreased synthesis and secretion of PTH. […] Infiltrative causes include destruction of the parathyroid glands secondary to granulomatous infiltration (eg, Riedel thyroiditis, amyloidosis, sarcoidosis). […] Metastatic cancer cells infiltrate the parathyroid gland leading to hypoparathyroidism. […] Wilson disease causes hypoparathyroidism due to copper infiltration and destruction of parathyroid glands. […] Hemochromatosis is an inherited disorder resulting in increased iron deposition in various organs, including the parathyroid glands, which leads to parathyroid gland dysfunction. […] Functional hypoparathyroidism is caused by hypomagnesemia as well as hypermagnesemia, both of which impair parathyroid function.

• #2 Hypoparathyroidism – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hypoparathyroidism/symptoms-causes/syc-20355375

  Low levels of magnesium in the blood. Low magnesium levels can affect the function of the parathyroid glands. Normal magnesium levels are required for normal production of parathyroid hormone. […] Extensive cancer radiation treatment of the face or neck. Radiation can result in destruction of the parathyroid glands. In rare cases, radioactive iodine treatment for hyperthyroidism may lead to hypoparathyroidism.

• #2 Inflammation-induced hypoparathyroidism triggered by combination immune checkpoint blockade for melanoma | Journal for ImmunoTherapy of Cancer | Full Text

  https://jitc.biomedcentral.com/articles/10.1186/s40425-019-0528-x

  Treatment with a combination of PD-1 and CTLA-4 targeted checkpoint inhibition has improved outcome of melanoma patients and led to durable remissions but is also associated with significant toxicities. […] Endocrinopathies affecting the parathyroid gland are rarely reported and no clear pathomechanism has been proposed. […] Our report demonstrates a rare endocrinopathy as a complication of combined PD-1 and CTLA-4 blockade. In addition, it provides evidence from the course of the disease that inflammation within the parathyroid gland is involved in the mechanism. […] Immune-mediated endocrinopathies are among the most common irAEs. […] Hypocalcemia has been found to be significantly associated with PD-1 inhibitor pembrolizumab treatment in a recent meta-analysis by Manohar et al. […] To our knowledge, there are only two case reports to date on severe hypocalcemia with confirmed hypoparathyroidism – one in a melanoma patient associated with nivolumab/ipilimumab treatment and another in a small cell lung cancer patient on nivolumab treatment.

• #2 Pediatric Hypoparathyroidism: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/922204-overview

  Hypoparathyroidism results from defective synthesis or secretion of parathyroid hormone (PTH), end-organ resistance, or inappropriate regulations that result from the activated or antibody-stimulated calcium-sensing receptor (CaSR). […] The net effects of PTH activity are an increase in serum calcium and a decrease in serum phosphate. PTH acts directly on bone to stimulate bone resorption and cause calcium and phosphate release. […] Hypoparathyroidism results in loss of both the direct and indirect effects of PTH on bone, the kidney, and the gut. Calcium and phosphate release from bone is impaired, calcium absorption from the gut is limited, calciuria develops despite hypocalcemia, and retention of phosphate from the urine causes increased plasma phosphate levels. […] Defects in PTH action occur in PHP. The hallmark of PHP is PTH resistance.

• #2 Hypoparathyroidism presenting with late onset seizures – a report of two cases from rural India

  https://www.oaepublish.com/articles/2347-8659.2017.65

  Acquired chronic hypoparathyroidism is generally the after effect of unintentional surgical removal of all the parathyroid glands. […] The essential capacity of PTH is to keep up the extracellular fluid (ECF) calcium concentration within a normal narrow range. […] Hypocalcemia produces hyperexcitability of nerve fibers with spontaneous and repetitive discharges. […] Seizures are a frequent complication: they have been reported in 20%-25% of patients with acute hypocalcemia and in 30%-70% of patients with idiopathic hypoparathyroidism. […] Seizures are thought to occur due to hypocalcemia and intracranial calcification that occur in vascular and perivascular locations. […] Eaton et al. in 1939 first described basal ganglia calcification (BGC) in association with chronic hypoparathyroidism. Pathogenesis is obscure, but its occurrence with hypocalcemia signifies an important role of increased calcium-phosphorus complex formation.

• #2 Basal ganglia calcification in idiopathic hypoparathyroidism | British Columbia Medical Journal

  https://bcmj.org/articles/basal-ganglia-calcification-idiopathic-hypoparathyroidism

  Hypoparathyroidism refers to a group of disorders in which extracellular calcium levels cannot be maintained within the normal range due to relative or absolute deficiency of parathyroid hormone. […] The most common causes of pathological BGC are hypoparathyroidism and pseudo-hypoparathyroidism. […] Pathogenesis is unknown, but its occurrence with hypocalcemia suggests that increased calcium-phosphorus complex formation plays a role. […] Basal ganglia calcification in idiopathic hypoparathyroidism is a progressive disorder and has been observed to worsen despite maintenance of normal calcium levels. […] These findings suggest that early diagnosis and strict control of phosphorus is another crucial component in treating and preventing progression of BGC. […] Despite some uncertainty about the exact pathogenesis of BGC, treatment is known to prevent progression.

• #2 How Hypoparathyroidism May Affect Your HeartEnvelope icon

  https://hypoparathyroidismnews.com/health-insights/how-hypoparathyroidism-may-affect-your-heart/

  The exact mechanism of how hypoparathyroidism can lead to heart problems is not clear. Researchers think that arrhythmias may be due to hypocalcemia (low levels of calcium). Calcium is an important molecule for the function of the nervous system and the ability of heart muscles to contract. Low levels of calcium can lead to trouble with signals from the autonomic nervous system to the heart. It also may cause changes in the flow of signals between heart cells, leading to an irregular rhythm.

• #2 Increased arterial stiffness in normotensive individuals with hypoparathyroidism | Scientific Reports

  https://www.nature.com/articles/s41598-025-92708-z

  Two previous studies described an association between hypoparathyroidism and mortality, while hyperphosphatemia and Ca x P product were found to be risk factors for fatal outcomes. […] The positive correlation between phosphorus level and the Ca x P product and PWV suggests that AS may be due to an increment in vascular calcification. […] The present study demonstrated an increase of AS in hypoparathyroidism patients, which is a reliable indicator for CVD risk.

• #2 Pediatric Hypoparathyroidism: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/922204-overview

  PHP Ia is due to loss-of-function mutations of the subunit of the G proteincoupled calcium-sensing receptor (Gsa). […] PHP and PPHP are manifestations of imprinting of the stimulatory G protein defect located on chromosome arm 20q. […] PHP Ib arises from epigenetic defects in the imprinted gene GNAS, which encodes the alpha subunit of the stimulatory G protein and the NESP55 protein. […] PHP II: Patients with PHP II have normal physical appearance. There is no association with the AHO phenotype. The genetic basis of PHP II is unknown. The defect appears to lie downstream of the signal for cAMP generation because PTH causes an increase in urinary cAMP without the phosphaturia that normally accompanies PTH stimulation.

• #2 Hypoparathyroidism: Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/22672-hypoparathyroidism

  Your parathyroid glands need magnesium, a type of electrolyte in your blood, to function properly. Because of this, low levels of magnesium (hypomagnesemia) can cause hypoparathyroidism. […] The goal of treatment for hypoparathyroidism is to minimize symptoms and correct the amount of calcium and minerals in your body. […] Most people with hypoparathyroidism have to take calcium and vitamin D supplements for life. […] Long-term use of parathyroid hormone injections may cause osteosarcoma, a type of bone cancer.

• #2 Treatment of Hypoparathyroidism by Re-Establishing the Effects of Parathyroid Hormone

  https://www.e-enm.org/journal/view.php?doi=10.3803/EnM.2024.1916

  Treatment with PTH, as a daily subcutaneous injection with recombinant human PTH(1-84) (rhPTH[1-84]), was marketed in 2015 for adults with chronic HypoPT that cannot be well controlled by treatment with calcium supplements and active forms of vitamin D alone. […] However, despite replacement therapy with rhPTH(1-84), the randomized controlled trial did not show a significant reduction in renal calcium excretion. […] Treatment with PTH(1-34) has to be injected twice a day in children and adults to maintain normocalcemia in patients with HypoPT. […] Palopegteriparatide is a prodrug with sustained release of PTH(1-34) designed to provide stable PTH levels in the physiological range for 24 hours/day. […] Eneboparatide is a long-acting PTH analog that acts as a PTH receptor 1 agonist, which through a novel mechanism of action activates a specific conformation of the receptor.

• #2 The PGRIS and parathyroid splinting concepts for the analysis and prognosis of protracted hypoparathyroidism – Sitges-Serra – Gland Surgery

  https://gs.amegroups.org/article/view/16238/html

  The fact that in ours and other authors experience the prevalence of permanent hypoparathyroidism in PGRIS 4 patients is in the 23.5% range, indicates that the parathyroid function not only depends on PGRIS but on the functionality of the remaining glands. […] We have put forward the hypothesis that this may favor restoration of the parathyroid function by inducing parathyroid metabolic rest after intraoperative injury (parathyroid splinting). […] Current data suggest that aggressive medical therapy of post-thyroidectomy hypocalcemia may enhance the restoration of the parathyroid function and improve long-term outcomes.

• #2 SciELO Brazil – Hypoparathyroidism and pseudohypoparathyroidism: etiology, laboratory features and complications Hypoparathyroidism and pseudohypoparathyroidism: etiology, laboratory features and complications

  https://www.scielo.br/j/aem/a/kf9fRZjjYhpM7NjByF6VPrD/

  In order to avoid these complications, maintenance of serum calcium around the lower limit and serum phosphate around the upper limit of normal ranges is recommended. In addition, the annual measurement of 24-hour urine calcium is encouraging for ruling out hypercalciuria, as well as renal ultrasound to diagnose nephrolitiases and nephrocalcinosis. However, it is a challenge to achieve these therapeutic goals, maintaining patients without symptoms, since HP is a chronic disease, and requires long life treatment. Recently, PTH 1-84 has been used in HP treatment in some countries. This new treatment may lead to control of calcemia without the exposure to high loads of calcium, and therefore may reduce urinary calcium excretion and consequently decrease the incidence of renal complications.

• #2 Inflammation-induced hypoparathyroidism triggered by combination immune checkpoint blockade for melanoma | Journal for ImmunoTherapy of Cancer | Full Text

  https://jitc.biomedcentral.com/articles/10.1186/s40425-019-0528-x

  Autoimmune hypoparathyroidism can be caused by either immune-mediated destruction or by hyperactivation of the CaSR by activating autoantibodies. Interestingly, we find that the hypoparathyroidism in the described patient was dependent on immune-suppressive medication and therefore was rather inflammation-mediated. […] Our case report therefore also provides a new insight into the pathomechanism of this rare side effect of ICI treatment.

• #2 Review of clinical practice guidelines for hypoparathyroidism | Kovaleva | Problems of Endocrinology

  https://www.probl-endojournals.ru/jour/article/view/12800/0?locale=en_US

  Hypoparathyroidism is a rare disorder characterized by the absent or inappropriately decreased serum parathyroid hormone in the parathyroid glands, which is accompanied by impaired calcium-phosphorus metabolism. […] The main etiology of hypoparathyroidism remains damage or removal of the parathyroid glands during neck surgery. […] Autoimmune hypoparathyroidism is the second most common form of the disease, usually occurring as part of type 1 autoimmune polyglandular syndrome. […] Chronic hypoparathyroidism of any etiology requires lifelong multicomponent therapy, as well as careful monitoring and an individual approach to choose the optimal treatment strategy. […] In the absence of adequate follow-up, the risks of long-term complications significantly increase, particularly in the renal, cardiovascular systems; in the soft tissues and in the brain, it could lead to visual disturbances; pathology of the musculoskeletal system with a decreased bone remodeling and a potential risk of fractures, as well as to the neurocognitive disorders and an impaired health-related quality of life.

• #3 Pediatric Hypoparathyroidism: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/922204-overview

  Hypoparathyroidism results from defective synthesis or secretion of parathyroid hormone (PTH), end-organ resistance, or inappropriate regulations that result from the activated or antibody-stimulated calcium-sensing receptor (CaSR). […] The net effects of PTH activity are an increase in serum calcium and a decrease in serum phosphate. PTH acts directly on bone to stimulate bone resorption and cause calcium and phosphate release. […] Hypoparathyroidism results in loss of both the direct and indirect effects of PTH on bone, the kidney, and the gut. Calcium and phosphate release from bone is impaired, calcium absorption from the gut is limited, calciuria develops despite hypocalcemia, and retention of phosphate from the urine causes increased plasma phosphate levels. […] Defects in PTH action occur in PHP. The hallmark of PHP is PTH resistance.

• #3 Postsurgical Hypoparathyroidism: A Systematic Review | In Vivo

  https://iv.iiarjournals.org/content/30/3/171

  Hypoparathyroidism (PHypo) is a relatively uncommon disease. Its main characteristics are hypocalcaemia, elevated serum phosphorus levels and low or inappropriately normal plasma levels of parathyroid hormone (PTH). […] PHypo results in hypocalcaemia because PTH secretion is impaired and cannot mobilize calcium from bone. Moreover, in the kidney, lower PTH levels result in lower Ca2+ reabsorption and lower Pi excretion in the urine and reduced or absent hydroxylation of 25-hydroxyvitamin D3 at the 1-position, leading to less formation of calcitriol. […] Parathyroid secretory reserve is abundant, thus, significant injury must occur before PHypo develops. It is estimated that one normal gland is adequate for the preservation of calcium homeostasis. […] The central function of PTH is to regulate ionized [Ca2+] levels by concerted effects on three principal target organs: bone, kidney and intestinal mucosa. In a normal individual, PTH stimulates bone resorption and the release of Ca+2 into the circulation.

• #3 Hypoparathyroidism — Knowledge Hub

  https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/hypoparathyroidism/

  Hypoparathyroidism is a rare disease characterised by hypocalcaemia due to deficiency of parathyroid hormone (PTH), usually following surgical removal or damage to the parathyroid glands. […] The TBX1 gene is included in the deletion. TBX1 is a transcription factor involved in parathyroid development and is thought to be the gene responsible for the hypoparathyroidism. […] GATA3 is a transcription factor and developmental gene involved in parathyroid gland development. […] The AIRE gene encodes a transcriptional regulator involved in thymic induction if immunologic self-tolerance. […] This condition is caused by a variety of PTH gene variants that can lead to aberrant processing or secretion of the hormone or a less biologically active hormone. […] This condition is caused by homozygous loss-of-function or heterozygous dominant negative variants in GCM2, a transcription factor gene that functions as a developmental gene for the parathyroid glands.

• #3 Hypoparathyroidism | MedLink Neurology

  https://www.medlink.com/articles/hypoparathyroidism

  Causes of hypoparathyroidism include surgery, autoimmune disorders, genetic diseases, hemochromatosis, magnesium deficiency, and idiopathic causes. […] Autoimmune invasion and destruction is the most common nonsurgical cause of hypoparathyroidism; it can be isolated or can occur as part of autoimmune polyendocrine syndromes. […] Hypoparathyroidism can be caused by mutations in several different genes. […] Pseudohypoparathyroidism is characterized by end-organ resistance to PTH. […] Ectopic calcification in brain tissues is seen with chronic hypocalcemia, as occurs with hypoparathyroidism and pseudohypoparathyroidism. […] Some cases with such brain calcifications may develop extrapyramidal and cerebellar dysfunction, seizures, cognitive impairment, or behavioral abnormalities.

• #3 Increased arterial stiffness in normotensive individuals with hypoparathyroidism | Scientific Reports

  https://www.nature.com/articles/s41598-025-92708-z

  The aim of the present research was to evaluate whether central hemodynamic parameters, particularly AS, are altered in post-surgical hypoparathyroidism patients and investigate any association between calcium metabolism parameters and AS. […] The present study evaluated the AS by PWV in patients with post-surgical hypoparathyroidism. […] Clinical, BP and laboratorial parameters investigated in this study demonstrated that hypoparathyroidism is associated with higher BP and AS, thereby contributing to increased cardiovascular risk. […] According to multivariate linear regression analysis, ionized calcium, phosphorus, and the Ca x P product are independent predictors for PWV. […] Although the present study demonstrated that calcium, phosphorus and the Ca x P product were adequate in serum, these parameters were correlated to AS.

• #3 Treatment of Hypoparathyroidism by Re-Establishing the Effects of Parathyroid Hormone

  https://www.e-enm.org/journal/view.php?doi=10.3803/EnM.2024.1916

  Treatment with PTH, as a daily subcutaneous injection with recombinant human PTH(1-84) (rhPTH[1-84]), was marketed in 2015 for adults with chronic HypoPT that cannot be well controlled by treatment with calcium supplements and active forms of vitamin D alone. […] However, despite replacement therapy with rhPTH(1-84), the randomized controlled trial did not show a significant reduction in renal calcium excretion. […] Treatment with PTH(1-34) has to be injected twice a day in children and adults to maintain normocalcemia in patients with HypoPT. […] Palopegteriparatide is a prodrug with sustained release of PTH(1-34) designed to provide stable PTH levels in the physiological range for 24 hours/day. […] Eneboparatide is a long-acting PTH analog that acts as a PTH receptor 1 agonist, which through a novel mechanism of action activates a specific conformation of the receptor.

• #3 Etiology and Pathophysiology of Hypoparathyroidism: A Narrative Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10364481/

  The approach utilized a systematic review of the medical literature executed with specifically designed criteria that focused on the etiologies and pathogenesis of hypoparathyroidism. […] Nonsurgical etiologies account for a significant proportion of cases of hypoparathyroidism (~25%), and among them, genetic etiologies are key. […] Approximately 25% of adults with hypoparathyroidism have a developmental, genetic, autoimmune, metabolic, or environmental condition that impairs either the secretion or action of PTH or alters parathyroid gland mass. […] Autoimmune hypoparathyroidism can occur as an isolated endocrinopathy or as a part of the autoimmune polyglandular syndrome type I (APS-1), a genetic disorder caused by mutations in the autoimmune regulator (AIRE) gene. […] The genetic disorders that are associated with hypoparathyroidism are discussed more fully elsewhere. […] The mechanism underlying the profound increase in bone mass in hypoparathyroidism is not clearly understood. […] Many etiologies for hypoparathyroidism have been identified, but the pathogenesis is unexplained in a large number of patients.

• #4 Hypoparathyroidism – Wikipedia

  https://en.wikipedia.org/wiki/Hypoparathyroidism

  Hypoparathyroidism is decreased function of the parathyroid glands with underproduction of parathyroid hormone (PTH). […] The parathyroid glands are so named because they are usually located behind the thyroid gland in the neck. They arise during fetal development from structures known as the third and fourth pharyngeal pouch. The glands, usually four in number, contain the parathyroid chief cells that sense the level of calcium in the blood through the calcium-sensing receptor and secrete parathyroid hormone. Magnesium is required for PTH secretion. Under normal circumstances, the parathyroid glands secrete PTH to maintain a calcium level within normal limits, as calcium is required for adequate muscle and nerve function (including the autonomic nervous system). […] PTH acts on several organs to regulate calcium levels and phosphorus levels. PTH acts on the kidneys to increase calcium reabsorption into the blood, and to inhibit phosphorus reabsorption (which causes phosphorus to be lost in the urine). It increases calcium and phosphorus absorption in the bowel indirectly by stimulating the kidneys to produce vitamin D which then acts on the gut. PTH also causes increase bone resorption which leads to the releases calcium and phosphorus into the blood.

• #4 Hypoparathyroidism — Knowledge Hub

  https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/hypoparathyroidism/

  This condition is caused by a complex deletion-insertion near the SOX3 gene, which is a transcription factor involved in parathyroid gland development. […] Management of patients with hypoparathyroidism is complex and should be undertaken by a multidisciplinary team. […] Ongoing gene-directed therapies and trials are investigating the use of rhPTH1-84, rhPTH1-34 and other novel PTH analogues, as well as possible gene therapy for PTH replacement.

• #4 Treatment of Hypoparathyroidism by Re-Establishing the Effects of Parathyroid Hormone

  https://www.e-enm.org/journal/view.php?doi=10.3803/EnM.2024.1916

  Encaleret is an oral CaSR antagonist (calcilytic), thereby addressing the underlying molecular pathophysiological mechanism. […] Despite normalizing plasma calcium levels, thereby alleviating severe symptoms of hypocalcemia, conventional treatment of HypoPT with active vitamin D and calcium supplements is associated with unpredictable fluctuations in plasma calcium levels, hypercalciuria, and several complications, including an increased risk of impaired kidney function and impaired QoL. […] Substitution with the missing hormone using rhPTH(1-84) or PTH(1-34) has been shown to reduce the need for conventional therapy; however, due to the short duration of action, replacement therapy with these analogues is not ideal. […] Treatment with eneboparatide and encaleret also seems to cause long-acting effects on the calcium-PTH axis, and phase 3 clinical trials are currently ongoing aiming to demonstrate a normalization of calcium homeostasis in response to treatment of patients with chronic HypoPT.

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