Neonatal Hypoparathyroidism Research Articles

Neurodegeneration: Microglia: Nf-Kappab Signaling Pathways.

Microglia is cells of mesodermal/mesenchymal origin that migrate into the central nervous system (CNS) to form resident macrophages inside the special brain microenvironment. Intact with both neuronal and non-neuronal cells, microglia is highly active cells. Continuous process extension and retraction allows microglia to scan the brain parenchyma for threats. They are also able to change their morphology from ramified to amoeboid, which is a sign of cell activity. In response to pleiotropic stimuli such as neurotransmitters, cytokines, and plasma proteins, microglia express a diverse range of receptors. As controllers of synaptic activities and phagocytosis of developing neurons, they serve a critical role in the healthy brain and have significant effects on synaptic plasticity and adult neurogenesis. A frequent cause of hypoparathyroidism is a mutation in the gene glial cells missing-2 (GCM2). Neonatal hypoparathyroidism has an amorphic recessive GCM2 mutation, while autosomal dominant hypoparathyroidism has a dominant-negative GCM2 mutation. Curiously, familial isolated hyperparathyroidism has been associated with activating GCM2 mutation. In addition to seizures, neurocognitive impairment, carpopedal spasm, tingling and numbness are common clinical manifestations of hypoparathyroidism. Biogenic amines are a group of four neurotransmitters that belong to that category and these include serotonin, dopamine, norepinephrine, and epinephrine. Numerous antidepressants prevent the reuptake from occurring the brain-gut axis is hardwired through the CNS, enteric nervous system (ENS), neuroendocrine linkages and highly innervated nerve plexuses.

Late-Onset Neonatal Hypocalcemia Due to Transient Hypoparathyroidism in Infant of Mother With COVID-19 at Delivery

Introduction: Neonatal hypocalcemia is an uncommon condition but clinical presentation can include severe manifestations such as neuromuscular irritability, tetany, seizure or cardiac conduction abnormalities that require prompt intervention to normalize calcium levels. To our knowledge there have been no reports of neonatal hypocalcemia following maternal SARS-CoV2 infection at the time of birth. Here we report a case of transient late-onset neonatal hypocalcemia complicated by maternal SARS-CoV-2 infection at the time of delivery.Clinical Case: A 13-day old full-term appropriate for gestational age female was born to an asymptomatic mother who tested positive for SARS-CoV2 at the time of delivery. Caretakers noticed minor twitching movements in the first few days of life that were progressively worsening. Initial ionized calcium was 0.6 mmol/L, and labs at time of transfer to our hospital were notable for total calcium of 5.5mg/dL(n 8.9–9.9), and ionized calcium of 0.67mmol/L (n 1.12–1.37 mmol/L). Calcium levels improved after she received IV calcium boluses and was started on continuous IV calcium infusion. Initial phosphorus was 8.3 mg/dL (n 3.2–7.4 mg/dL) and magnesium was 1.2 mg/dL (n 1.5–2.2 mg/dL), while intact PTH was inappropriately low at 12.2 pg/mL (n 10–65 pg/mL), and urine calcium to urine creatinine ratio was below the limits of assay detection (n <0.86), consistent with a diagnosis of neonatal hypoparathyroidism. The 25-hydroxy vitamin D was 11.1 ng/mL (n 30–100 ng/mL), which may have also been a contributing factor. She had no dysmorphic features on examination concerning for 22q deletion syndrome, and tested negative for SARS-CoV2. Chromosomal microarray did not reveal clinically relevant copy number alterations or areas of homozygosity. Calcium stabilized on enteral calcium carbonate, calcitriol, and cholecalciferol, and she was weaned off of all supplementation. Prior to discharge PTH recovered to 36.9 pg/ml with a calcium of 9.9 mg/dL, phosphorus 7.7 mg/dL, normal magnesium and 25-hydroxy vitamin D (31.3 ng/ml). She was discharged on Similac PM 60/40 formula to reduce her dietary phosphorus content, and 400 IU of cholecalciferol.Conclusions: Hypocalcemia in patients with severe COVID-19 is being increasingly reported. There is minimal data on the effect of perinatal SARS-CoV2 infections on neonatal health. While this report does not establish causation, expanding awareness of neonatal abnormalities following maternal SARS-CoV2 infection at delivery will help to recognize causal associations and improve patient care.

Hypercalcaemia during pregnancy: Review of maternal and fetal complications, investigations, and management.

Asymptomatic mild primary hyperparathyroidism is increasingly being identified during pregnancy. Recent studies have demonstrated inconsistent findings with regard to pregnancy complications and the need for surgical intervention during pregnancy. A retrospective audit of outcomes of pregnancies complicated by hypercalcaemia over a 15-year period was performed. Twenty-nine pregnancies to 26 women with hypercalcaemia were identified, corresponding to 37 cases per 100,000 deliveries. Hypercalcaemia was due to primary hyperparathyroidism in 90% of cases, with mean serum calcium of 2.89 mmol/l and mean ionised calcium 1.43 mmol/l. Four women underwent successful neck exploration during pregnancy. Pregnancy complications were limited to three cases of pre-eclampsia and one case of symptomatic neonatal hypoparathyroidism. Close observation without surgical intervention would seem reasonable in women with mild hypercalcaemia during pregnancy.

Neonatal Hypocalcemic Seizures Due to Excessive Maternal Calcium Ingestion

Hypocalcemia is a common, treatable cause of neonatal seizures. A term girl neonate with no apparent risk factors developed seizures on day 5 of life, consisting of rhythmic twitching of all extremities in a migrating pattern. Physical examination was normal except for jitteriness. Laboratory evaluation was unremarkable except for decreased total and ionized serum calcium levels and an elevated serum phosphorus level. The mother had ingested 3-6 g of calcium carbonate daily during the final 4 months of pregnancy to control morning sickness. The baby's electroencephalogram showed multifocal interictal sharp waves and intermittent electrographic seizures consisting of focal spikes in the left hemisphere accompanied by rhythmic jerking of the right arm and leg. Treatment with intravenous calcium gluconate over several days resulted in cessation of seizures and normalization of serum calcium. The child has remained seizure free and is normal developmentally at 9 years of age. Hypocalcemic seizures in this newborn were likely secondary to excessive maternal calcium ingestion, which led to transient neonatal hypoparathyroidism and hypocalcemia. Inquiry about perinatal maternal medication use should include a search for over-the-counter agents that might not be thought of as "drugs," as in this case, antacids.

Seizures in an Arabian foal due to suspected prolonged transient neonatal hypoparathyroidism

SummaryThis Case Report describes a 5‐week‐old male Arabian foal of Egyptian bloodline with generalised seizures due to hypocalcaemia. The laboratory changes in this foal were consistent with an abnormal regulation of calcium as occurs with hypoparathyroidism. Prolonged transient neonatal hypoparathyroidism as reported in man was suspected. The foal received oral calcium and vitamin D3 supplementation combined with the calcium sparing diuretic carbonic anhydrase inhibitor acetazolamide. Calcium concentrations increased gradually over 6 months. In Arabian foals, especially those of Egyptian bloodline suffering suspected juvenile epilepsy, hypocalcaemia should be ruled out as a cause of seizures.

Transient neonatal hypoparathyroidism in two siblings unmasking maternal normocalcemic hyperparathyroidism

Hypoparathyroidism is one of the recognized causes of late-onset neonatal hypocalcemia. Maternal hypercalcemic hyperparathyroidism has been shown to suppress fetal parathyroid glands, causing transient neonatal hypoparathyroidism. We report two siblings (6 years apart) with transient hypoparathyroidism presented with hypocalcemic seizures during the first 2 weeks of life. Subsequent investigation revealed an unrecognized normocalcemic hyperparathyroidism with nephrocalcinosis in the mother. Maternal hyperparathyroidism was caused by two parathyroid adenomas. In conclusion, our report highlights the importance of careful evaluation of neonatal hypoparathyroidism in uncovering an unrecognized, asymptomatic hyperparathyroidism in the mother.

The spectrum of parathyroid gland dysfunction associated with the microdeletion 22q11

Clinical features associated with microdeletion of chromosome 22q11 (del(22)(q11)) are highly variable. Increased awareness of this condition is needed among specialists such as endocrinologists to reduce diagnostic delay and improve clinical care. The purpose of this study was to describe the phenotype of patients with del(22)(q11), focusing on parathyroid gland dysfunction. Charts of 19 patients, including one kindred of three, known to have del(22)(q11) diagnosed by fluorescence in situ hybridization (FISH) were reviewed from the register of the department of Medical Genetics. Major clinical features including hypoparathyroidism phenotype were collected. Parathyroid dysfunction was present in 8 out of 16 patients (50%). Six patients were diagnosed with overt hypoparathyroidism. Hypocalcemia manifested as laryngeal stridor within the first days of life (n = 3), seizures in infancy (n = 1) and adolescence (n = 2). The connection between hypoparathyroidism and diagnosis of del(22)(q11) was belated at the median age of 18 years. One patient had presented with transient neonatal hypoparathyroidism, and one patient had latent hypoparathyroidism. Within the kindred family, the phenotype variability including that of parathyroid dysfunction was as marked as between unrelated individuals. Standard karyotype failed to detect the deletion in 15 out of 19 cases. Abnormal parathyroid function in the del(22)(q11) ranges from severe neonatal hypocalcemia to latent hypoparathyroidism. Del(22)(q11) should be considered as a potential cause of hypocalcemia even in young adult. When suspected, the diagnosis requires investigation by FISH. Furthermore, long-term calcemia follow-up is needed in normocalcemic patients with del(22)(q11) because of the possible evolution to hypocalcemic hypoparathyroidism.

Index of Suspicion In the Nursery

A 9-day-old Hispanic boy presents to the emergency department with seizures and apnea. The seizure lasts for about 3 minutes and is characterized by stiffening of the body and laryngospasm. Laboratory evaluation reveals a serum calcium concentration of 6 mg/dL (1.5 mmol/L). Hypocalcemic tetany resolves after administration of intravenous calcium. The infant also has fever of 100.4°F (37.7°C). The infant was born at term, and his birthweight was 3.2 kg. He is the fifth child born of nonconsanguineous parentage. The antenatal period was uneventful. Because the family does not have insurance, the mother had not taken prenatal vitamins and supplements. The baby has been fed with human milk and formula. On physical examination upon admission to the hospital, his temperature is 99°F (36.9°C), pulse is 186 beats/min, respiratory rate is 54 breaths/min, blood pressure is 97/64 mm Hg, and weight is 3.83 kg. He has no dysmorphic features and is normocephalic, with an open and flat anterior fontanelle without craniotabes. No cataracts or Chvostek sign are present. Cardiovascular examination reveals a regular heart rate and rhythm, with no murmurs. The lungs are clear to auscultation bilaterally, and there is no hepatosplenomegaly. Neurologic findings are normal. Laboratory evaluation reveals: sodium, 136 mEq/L (136 mmol/L); potassium, 5.2 mEq/L (5.2 mmol/L); chloride, 101 mEq/L (101 mmol/L); bicarbonate, 26 mEq/L (26 mmol/L); blood urea nitrogen, 10 mg/dL (3.57 mmol/L); creatinine, 0.3 mg/dL (26.5 mcmol/L); glucose, 109 mg/dL (6.1 mmol/L); calcium, 6.6 mg/dL (1.65 mmol/L); phosphorous, 10.5 mg/dL (3.4 mmol/L); albumin, 3.0 g/dL (30 g/L); and magnesium, 2 mg/dL (0.82 mmol/L). The white blood cell count and differential count are normal. Findings on cerebrospinal fluid evaluation are normal. However, the 25-hydroxyvitamin D concentration is less than 7 ng/mL (17.5 nmol/L) (normal, 10 to 68 ng/mL [25 to 169.7 nmol/L]), the 1,25-dihydroxyvitamin D concentration is 45 …

Autosomal/Recessive Hypocalciuric Hypercalcemia

Letters15 May 1997Autosomal/Recessive Hypocalciuric HypercalcemiaH.J. Van PeenenH.J. Van PeenenSalem, OR 97302Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-10-199705150-00040 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Dr. Dunn is, of course, correct. In the poem, I am indeed referring to a child inheriting a dominant gene from each parent. Familial hypocalciuric hypercalcemia (FHH) is normally a very mild condition that is dominant with variable penetrance. There are multiple defective alleles. Most people with mild forms of the disease are asymptomatic and undiagnosed, hence the reference in the poem to random matings.The poem was inspired by the recent discovery that severe neonatal hypoparathyroidism is an extreme example of FHH, caused by a double dose of mutations at the human calcium-ion sensing receptor gene [1]. ...REFERENCE1. Pollak MR, Chou YH, Marx SJ, Steinmann B, Cole DE, Brandi ML, et al. Familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Effects of mutant gene dosage on phenotype. J Clin Invest. 1994; 93:1108-12. Google Scholar Author, Article, and Disclosure InformationAffiliations: Salem, OR 97302 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 May 1997Volume 126, Issue 10Page: 835KeywordsAllelesHypercalcemiaHyperparathyroidismHypoparathyroidismMutation Issue Published: 15 May 1997 CopyrightCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...

Neonatal Hyperparathyroidism and Skeletal Demineralization in an Infant With Familial Hypocalciuric Hypercalcemia

Familial hypocalciuric hypercalcemia (FHH) is a benign dominantly inherited condition, in which the total and ionized calcium are maintained at values well above the normal range.1 When an affected mother is carrying an unaffected fetus, the fetus is chronically exposed to pathologically high calcium levels and neonatal hypoparathyroidism would be expected, as we2 and others have reported.3,4 Conversely, when a fetus is affected, but the mother is not, the fetus might be expected to develop hyperparathyroidism, which should manifest at birth. These infants may require emergency surgery5 or may be managed medically until the hyperparathyroidism subsides.6,7 We report here an infant with FHH, a first cousin of our previous case, who presented with hyperparathyroidism and skeletal demineralization.

Kenny-Caffey syndrome in two sibs born to consanguineous parents: evidence for an autosomal recessive variant.

We report on 2 sibs with manifestations of the Kenny-Caffey syndrome born to normal, consanguineous parents. Clinical manifestations included dwarfism, internal cortical thickening and medullary stenosis of tubular bones, poorly ossified skull bones, and hypocalcemia. The younger of the two died during a tonic convulsion. The older had neonatal hypoparathyroidism and is now a short intelligent, 1-year-old child. This family gives new support to the existence of an autosomal recessive variant of the syndrome.

1098 SYNERGISTIC EFFECT OF CALCIFEROL AND PARATHYROID HORMONE ON CALCIUM ABSORPTION IN NEWBORN RATS (NBR)

Serum calcium (CaS) in NBR was 9.0±.05 mg/dl at spontaneous or Caesarean delivery; maternal CaS was 8.7±.08. At 20 hr, CaS was 7.6±.13 in nursing NBR and 7.1±.07 in NBR gavaged with calciferolfree simulated rat milk(F). When F was supplemented with ergocalciferol (D2, 41U/rat=800IU/Kg) , CaS at 20 hr was 7.0±.05. When F contained 1-25(OH)2D3 (10 ng/rat=2μg/Kg), CaS at 20 hr was 8.1±.06. Ca-free F gave a 20 hr CaS of 6.9±.05; with 1-25(OH)2D3 CaS was 7.0±.08, indicating that enhancement of CaS by 1-25(OH) 2D3 was due to intestinal absorption rather than bone Ca mobilization. When F contained no D2, parathyroid extract (PTE, .05 ml 1M) at delivery had no effect on CaS at 20 hr (7.0±.08). On D2-supplemented F with PTE at delivery, 20-hr CaS was 7.4±.10. Absorption of Ca was increased by 1-25(OH)2D3 but not by D2. CaS increased when both D2 and PTE were given, suggesting that hypoparathyroidism rather than insufficient renal hydroxylase or unresponsive mucosa caused the lack of response to D2 alone. The feto-maternal CaS gradient indicates a placental pump which may account for neonatal hypoparathyroidism on the basis of intrauterine suppression, as has been inferred for human subjects. Insofar as these results apply to human newborns, they suggest that the effectiveness of 1-25(OH)2D3 in the amelioration of neonatal hypocalcemia derives from functional hypoparathyroidism rather than from renal or intestinal unresponsiveness.

1227 ENDOCRINE STUDIES IN OFFSPRING OF TERBUTALINE-TREATED MOTHERS

Terbutaline (T) a β2-sympathomimetic, has been extensively used; as a tocolytic agent in premature labor. To assess the influence of fetal β2-sympathomimetic stimulation upon glycemic (G) and calcemic (Ca) status, we compared the offspring of 12 women who had received T with 12 age and weight-matched infants of untreated mothers. Umbilical cord serum cortisol (F), insulin (I), growth hormone (GH), parathyroid hormone (PTH), calcitonin (CT) and glucagon (GLC) were measured by RIA. Mean GA at onset of T was 30.7 wks; 69% were treated for less than 48 hrs. Mean time from last dose of T was 6.7 hours. Age, weight and hormone data are listed below; means (±SE) do not differ. At 24 hours, serum Ca was lower (p<0.02) in T- treated (7.4±0.3) than in control babies (8.5±0.3). Previously reported β2-agonistinduced neonatal hypoglycemia was not demonstrated, presumably prevented by glucose infusions. In conclusion: 1) Differences did not exist in cord glucose, calcium and hormone levels. 2) T-treated offspring showed significant lowering of postnatal Ca, possibly due to exaggerated neonatal hypoparathyroidism secondary to adrenergic stimulation of maternal parathyroid glands.

847 NEONATAL HYPOCALCEMIA ASSOCIATED WITH MATERNAL HYPERCALCEMIA

An infant born to a mother with hypercalcemia secondary to metastatic breast cancer developed severe hypocalcemia during the first week of life. Maternal calcium and phosphorous levels ranged from 14-17 mg/dl and 2-2.5 mg/dl, respectively, prior to delivery, and the infant's calcium level was 15.0 mg/dl at birth. During the first 9 days of life the infant's serum Ca level decreased to 4.8 mg/dl and P rose to 8.4 mg/dl. The serum Mg decreased to 0.7 mg/dl. Administration of MgSO4 intramuscularly raised the serum Mg to normal levels, but hypophosphaturia and hypocalcemia persisted. Administration of PTH was followed by return of Ca to normal levels and an apparent increase in P excretion. When PTH was stopped, serum Ca and Mg again decreased, but the phosphaturia persisted. Ca and Mg levels returned to normal spontaneously by the fourth week of life. The hypocalcemia of this infant supports the hypothesis of transient neonatal hypoparathyroidism resulting from exposure to relatively high levels of maternal Ca in utero and contradicts the theory that it is related to Mg deficiency and end-organ unresponsiveness to PTH.

Plasma Inorganic Phosphate and Glucose of Prepubertal Children Taking Testosterone

It has been known for many years that the inorganic phosphate concentration of plasma is elevated in early life. 1-5 The high values found during the newborn period may result from a relatively high phosphorus intake, temporary neonatal hypoparathyroidism, low glomerular filtration rate, or a failure of the renal tubule to respond to parathyroid hormone. 1-5 After the first year of life, however, the elevation has been attributed by many to the presence of a high concentration of growth hormone. 6-9 Hamilton, Bunch, Mestler, and Imagawa recently reported that after orchiectomy the plasma inorganic phosphate of young adults rose to the prepubertal level within one to three weeks.10 They interpreted their data, and those from the literature, as indicating that sex hormones exert a depressant effect on the plasma phosphate concentration and concluded that sex hormones, rather than a decreasing concentration of growth hormones, may depress the phosphate concentration during