Estimation of Urinary Calcium as a Predictor of Pregnancy Induced Hypertension

Hypertensive diseases are still a leading cause of death among mothers all over the world. It’s complicated aetiology, which begins with aberrant placentation and ends with endothelial dysfunction, is yet unknown. The goal of this study is to learn about changes in serum and urine calcium levels in women who have Gestational Hypertension. 200 normotensive pregnant women between 24-28 weeks were included in the study based on inclusion and exclusion criteria. Urine calcium and creatinine and serum uric acid, total protein, albumin and serum sodium were estimated in corresponding samples collected from patients. The study showed a sensitivity of 80%, specificity of 71%, positive predictive value was 77%, negative predictive value 74%, and diagnostic accuracy as 74%. A single estimation of calcium to creatinine ratio in asymptomatic pregnant women between 24-28 week of gestation is a simple and cost-effective test.

Effect of Hydroalcholic Extract of Allium noeanum Reut. ex Regel on Ethylene Glycol- Induced Kidney Stone in Male Wistar Rats

We want to evaluate the effect of Allium noeanum Reut. ex Regel (Bonsor) known (traditional medicine agent) in calcium oxalate stones in kidney. 36 male rats were divided into 6 groups. I: healthy model + water, II: negative model + 1% ethylene glycol in water, III: 750 mg/kg of total extract +1% of ethylene glycol in water(Prevention), IV: 250 mg/kg flavonoid extract +1% of ethylene glycol in water (Prevention), V: 1500 mg/kg of total extract from 15th day+ 1% of ethylene glycol in water (Treatment), VI: 500 mg/kg of flavonoid extract from 15th of the study + 1% of ethylene glycol in water (Treatment).24-hour urine and blood samples were collected in 30th day for analysis. Pathology of kidneys was checked. Serum urea, uric acid, creatinine and urine calcium and oxalate were significantly increased, urine citrate was decreased in group II Vs I. (P < .05). Extract administration significantly decreased serum creatinine, urea and uric acid. Urine calcium and oxalate significantly decreased in treated groups. Urine calcium levels were significantly decreased in treated rats, but urine citrate levels were increased Vs group II. (P < .05). No crystal accumulation and tubular cast were observed in prevention groups. Hydroalcholic extract of Allium noeanum was able to reduce urine oxalate.

Spontaneous alteration of blood pH by a bicarbonate buffer system during experimental hypercalcaemia in cows

Introduction Maintaining mineral homeostasis as well as the secretion and metabolism of mineralotropic hormones is important for healthy of periparturient dairy cows. To increase the activity of mineralotropic hormones, blood pH can be adjusted. The purpose of this study was to investigate changes in blood pH and the mechanism of action of this change in induced hypercalcaemic cows. Material and Methods Six non-lactating Holstein cows were used in a 2 × 2 crossover design. To induce hypercalcaemia, calcium borogluconate was administered subcutaneously to experimental cows and normal saline was administered subcutaneously to control cows. Blood and urine samples were collected serially after administration. Whole blood without any anticoagulant was processed with a portable blood gas analyser. Plasma concentration and urinary excretion of calcium were measured. Results In hypercalcaemic cows, both blood and urine calcium levels were significantly increased at 8 h compared to those at 0 h (P < 0.05), and a spontaneous increase in blood pH was also observed. The calcium concentration in plasma was highest at 2 h after administration (3.02 ± 0.27 mmol/L). The change in pH correlated with that in bicarbonate (r = 0.781, P < 0.001) rather than that in partial pressure of CO2 (r = 0.085, P = 0.424). Conclusion Hypercalcaemia induced a spontaneous change in blood pH through the bicarbonate buffer system and this system may be a maintainer of calcium homeostasis.

Impact of Thyroid Disease on Bone Mineral Density Preservation in Patients With Osteoporosis and Idiopathic Hypercalciuria

Background: Idiopathic hypercalciuria (IHC) is associated with reduced bone mineral density (BMD) and increased risk of osteoporotic fractures. It is not known if thyroid disease impacts the degree of urine and bone mineral abnormalities in patients with IHC and osteoporosis (OPO). Methods: Retrospective chart review from a private endocrinology clinic identified 62 consecutive patients with OPO (fragility fracture and/or t-score ≤-2.5 on bone density scan) and concomitant diagnosis of IHC (urine calcium &gt; 4.0 mg/kg weight/d when intaking low-moderate calcium amounts). Patients were classified into two groups: those with thyroid disease (Thy+, if presence of autoimmune thyroid disease [AITD] with high antibody titers and/or long-term thyroid medication use) and those without (Thy-). Comparisons were made between the two groups for severity of renal disease (urine calcium) and bone disease (number of fragility fractures, and BMD response to therapy). Results: Of 55 women and 7 men identified with both OPO and IHC, 30 were Thy+ (4 with Graves’, 11 with confirmed Hashimoto’s, 13 taking levothyroxine for presumed Hashimoto’s and 2 with thyroid cancer), and 32 were Thy- (including 2 with type 1 DM, 1 with vitiligo, and 6 with non-toxic nodular goiters requiring biopsies). Thy+ were compared to Thy- with respect to: mean age (70.7 ± 7.3 vs. 70.8 ± 9.3 y), sex (97% vs. 81% women), 24-hr urine calcium at diagnosis (317 ± 75 vs. 311 ± 68 mg), presence of fragility fracture (50% vs. 59%), use of thiazide (83% vs. 78%), and use of anti-fracture pharmacotherapy (73% vs. 84%). 50 patients had adequate comparative longitudinal BMD data. A (+) BMD response was based on consistent increases in BMD and/or t-scores across all spine and hip sites, and a (-) BMD response was classified by decreased BMD and/or t-scores across all sites. For Thy+ vs. Thy- patients, there were 25% vs. 69% (+) BMD response, 38% vs. 12% (-) BMD response, 21% vs. 4% with no significant BMD response, and 17% vs. 15% with mixed BMD responses. Conclusions: In this group at high risk for future fragility fractures, much lower rates of BMD preservation was seen in the Thy+ as compared to the Thy- patients. Overall, AITD and medical thyroid disease was very common (48%) in this cohort of patients with IHC and OP. However, this high rate may be confounded by the selective nature of the specialty clinic population. Further research needs to delineate the impact of AITD and thyroid medication use on the progression and treatment of patients with IHC and OPO.

Presentation of Pheochromocytoma, Papillary Thyroid Cancer and Hyperparathyroidism in Three Family Members

Introduction: Although rare, one of the most common inherited disorders is multiple endocrine neoplasia. It is an autosomal dominant disorder that predisposes individuals to certain endocrine abnormalities depending on which type. The type 2A is a combination of medullary thyroid cancer, hyperparathyroidism, and pheochromocytoma which have been explained to be due to a mutation in the RET proto-oncogene. This abstract present a case of a patient with hyperparathyroidism whom family members also have pheochromocytoma and papillary thyroid cancer. Case description: A 45 year-old Hispanic male came to the endocrinology clinic complaining of constipation and headache. He has a personal history of non-toxic multinodular goiter and underwent right sided thyroidectomy in 2015 with pathology report showing follicular adenoma. He is currently on thyroid replacement therapy. He is clinically and biochemically euthyroid with TSH of 2.29 IU/ml. Physical examination was unremarkable. His labs were pertinent for calcium 11.5mg/dl, parathyroid 245.7pg/ml, creatinine of 1.5mg/dl. Two years ago, parathyroid was 189.5pg/ml and calcium was 11mg/dl, 1.5 year ago parathyroid level was 235.5pg/ml, calcium was 11.4mg/dl, urine calcium 9.3mg/dl, 24hr urine calcium 286.4mg, calcitonin &lt;2pg/ml, vitamin D 23ng/ml, 1,25 vitamin D 53ng/ml. In 2017, Sestambi scan showed equivocal focus of faint parathyroid activity in the region of the mid to lower left thyroid lobe versus faint residual thyroid activity and in 2019, scan showed no definite parathyroid adenoma. Surgical intervention was recently recommended due to patient’s DEXA scan showing osteoporosis of the femoral neck. The family history of this patient is pertinent for two sisters; one with pheochromocytoma and the other with papillary thyroid cancer. One of the sisters is a 60 years old diagnosed with pheochromocytoma at 51. Her free normetanephrine level was 682pg/ml and total metanephrine was 727pg/ml at time of diagnosis. Her MRI report showed right adrenal mass measuring 3.5x2.8cm. Laparoscopic right adrenalectomy was done and pathology confirmed pheochromocytoma which was RET negative. She still follows up with endocrinology and calcitonin, chromogranin A and plasma metanephrines have been normal. The second sister is now 53 years old diagnosed with papillary thyroid cancer at age 27 and had total thyroidectomy with pathology confirming papillary thyroid cancer. Discussion: Based on the clinical presentation of these family members, the most likely explanation is familial inheritance. This pattern of inheritance cannot be explained by MEN 2A or 2B due to the absence of medullary thyroid cancer. It has also been reported that this unusual presentation could be a variant of MEN 2A.[i] Due to the family history, close follow up is required to monitor for the possible development of other endocrinopathies in the future.

MO053GITELMAN'S SYNDROME AND PREGNANCY: TWO SUCCESSFUL CASE REPORTS

Background and Aims Gitelman’s Syndrome (GS) is a rare autosomal recessive hereditary salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. Pregnancy in women with GS often aggravates hypokalemia and hypomagnesemia. However, there are few reports of pregnancies in GS. Here, we report the course of two Chinese women who were diagnosed as GS during pregnancy in 2019 and 2020 respectively. Method Case 1: A 21-year-old woman was referred to our hospital at 9 weeks gestation of her first pregnancy. She had complained of muscle weakness and cramps for one year. Before the referral she was diagnosed as hypokalemia and treated by oral potassium supplementation. However, her symptoms became severer after pregnancy. Case 2: A 20-year-old woman was admitted to the hospital because of elevated plasma glucose level and hypokalemia at 27 weeks gestation of her first pregnancy. The woman was asymptomatic and denied history of chronic diseases. The laboratory examinations were taken after admission. Genetic testing was conducted for pathogenic mutations in SLC12A3 (GS) and SLC12A1, KCNJ1, CLCKNB and BSND (Bartter syndrome 1-4). Results Case 1: Initial biochemistry examinations revealed hypokalemia (2.3 mmol/L, normal range 3.5-5.3 mmol/L) with inappropriate renal potassium wasting (urine potassium 254 mmol/24h, normal range &lt; 20 mmol/24h), alkalosis (arterial blood gas pH 7.49), hypomagnesemia (0.55 mmol/L, normal range 0.67-1.04 mmol/L), hypocalciuria (urine calcium 1.6 mmol/24h, normal range 2.5-7.5 mmol/24h) and elevated renin (276 pg/ml, normal range 4-24 pg/ml) and aldosterone (825 pg/ml, normal range 10-160 pg/ml) levels. The blood pressure was normal-low (97/68 mmHg, 12.9/9.0 kPa) and the renal ultrasound was normal. Homozygous mutations [c.179C&gt;T (Thr60Met)] were identified. The woman’s father and sister had a heterozygous c.179C&gt;T, but had no electrolyte disorders. After the treatment of oral potassium supplementation (KCl 3g tid) and spironolactone (40mg bid), her serum potassium level increased to 3.4-4.0 mmol/L and muscle weakness was relieved. The woman delivered a healthy female infant weighing 2600 g at 39 weeks gestation via cesarean section. Maternal serum potassium level remained normal and no symptoms reoccured after delivery. Case 2: Initial biochemistry examinations identified hypokalemia (2.3 mmol/L, normal range 3.5-5.3 mmol/L) with inappropriate renal potassium wasting (urine potassium 81 mmol/24h, normal range &lt; 20 mmol/24h), hypomagnesemia (0.49 mmol/L, normal range 0.67-1.04 mmol/L), hypocalciuria (urine calcium 0.3 mmol/24h, normal range 2.5-7.5 mmol/24h) and elevated renin (54 pg/ml, normal range 4-24 pg/ml) and aldosterone (834 pg/ml, normal range 10-160 pg/ml) levels. The blood pressure and renal ultrasound were normal. Heterozygous mutations [c.179C&gt;T (Thr60Met), c.658G&gt;A (Gly220Ser)] were identified. The woman was treated by oral potassium supplementation (KCl 3g tid) and her serum potassium level maintained normal during pregnancy. She had a normal delivery of a healthy female infant weighing 3050 g at 40 weeks gestation. After delivery she discontinued oral potassium supplementation and her serum potassium level ranged from 3.0-3.4 mmol/L without symptoms. Conclusion The outcome of mother and fetus of GS pregnancies appears favorable. Intensive monitoring of electrolyte levels and sufficient electrolyte supplementation are advised during pregnancy.

Hypercalcemia With Non Suppressed Parathyroid Hormone in a Young Female- A Rare Case of Calcium Sensing Receptor Gene Related Familial Hypocalciuric Hypercalcemia-1

Background: Familial Hypocalciuric Hypercalcemia (FHH) is a rare disorder, associated with hypercalcemia and hypocalciuria and inherited in an autosomal dominant manner. Its true prevalence is unknown, and is estimated to be around 1 in 78,000 as compared to primary hyperparathyroidism (PHPT) which is around 1 in 1000. There are 3 mutations known to cause FHH. FHH-1 is caused by inactivating mutation in the calcium sensing receptor (CaSR) gene. Mutations associated with FHH-2 and FHH-3 are GNA11 and AP2S1 respectively. Case Presentation: 38-year-old female presented to endocrinology, for evaluation of hypercalcemia (10.8 mg/dL, with normal albumin). She was not on any calcium supplements or any other medications which can cause hypercalcemia. She did not have any prior fracture or nephrolithiasis or renal insufficiency. Her father reported to have hypercalcemia; no further evaluations of her father were available. Examination revealed an obese female with no skeletal or dental or other physical abnormalities. Laboratory evaluations: PTH= 37 pg/ml (15–65), 25 OH vitamin=D-30 pg/ml, Mg=2 mg/dL (1.5–2.6), phosphorus=3.1 mg/dl (2.5–4.8), 24 hour urine calcium=0.151 g/24 hours-with 24 hour urine calcium clearance of 0.008. Therefore, evaluations were highly suggestive of FHH. Subsequently, she had genetic evaluation which confirmed heterozygous CaSR mutation, confirming FHH-1. Her mother had genetic testing and was not found to have the mutation. So, it was concluded that the patient likely inherited the gene from her father, who also had hypercalcemia. She is being monitored clinically and with serial laboratory evaluations to monitor her calcium levels. Discussion: CaSR is expressed in parathyroid glands and kidneys which plays a key role in calcium regulation. CaSR inactivating mutation (seen in FHH-1) leads to hypocalciuria and hypercalcemia. 24 hour urine calcium clearance (urine Ca x serum Cr/ serum Ca x urine Cr) of &lt;0.01 is highly suggestive of FHH. Furthermore, higher concentration of calcium is required to suppress PTH release leading to high or nonsuppressed PTH. This finding can mislead towards the diagnosis of PHPT and unnecessary parathyroid surgery, if the diagnosis of FHH is missed. FHH is usually a benign disorder; subtotal parathyroidectomy does not cure the disease. FHH, rarely can cause atypical complications such as pancreatitis and total parathyroidectomy may be indicated to prevent further episodes of pancreatitis. Conclusions: This is a rare case presentation of hypercalcemia due to CaSR inactivating mutation related FHH. FHH and PHPT are competing diagnoses, when a patient presents with hypercalcemia and has nonsuppressed PTH. FHH is rare, however needs to be suspected in a young patient with family history of hypercalcemia, to avoid misdiagnosis of PHPT and unnecessary surgical intervention.