Elevated Parathyroid Hormone Levels Research Articles

A Therapeutic Approach to Primary Hyperparathyroidism: A Collaborative Evaluation Between Endocrinology and Surgery.

Introduction Primary hyperparathyroidism (PHPT) is a disorder in which one or more parathyroid glands overproduce parathyroid hormone, leading to hypercalcemia. It may present with symptoms likeconstipation, abdominal pain, psychiatric complaints as well as signs of nephrolithiasis, and osteoporosis that may need surgical treatment. PHPT is often underdiagnosed and undertreated. Our study aimed to review hypercalcemia in a single center to evaluate forundiagnosed PHPT. Methods A group of 546 patients from Southwest Virginia was selected using the EMR Epic (Epic Systems, Verona, USA)who had adiagnosis of hypercalcemia in the previous six months.Charts were manually reviewed, and patients were excluded based on the lack of hypercalcemia as well as previous testing of parathyroid hormone (PTH) levels. One hundred and fifty patients were excluded because of a lack of documented hypercalcemia. Letters were sent to the patients advising the patients to discuss whether a PTH would be indicated with their primary care provider (PCP). These patients' charts were re-examined six months later and a determination of whether a PTH level was performed as well as any referrals explicitly for hypercalcemia or PHPT was done. Results A total of 20 (5.1%) patients had a new PTH test during the time assessed. Of these patients, five received referrals to surgical treatment and six received referrals to endocrinology for treatment (no patients received referrals to both). Of those who obtained a PTH level, 50% of them had significantly elevated PTH levels consistent with the diagnosis of primary hyperparathyroidism. An additional 45% had levels of parathyroid hormone that were in the normal range but or most likely inappropriately normal for the concurrent level of calcium. Only one patient (5%) had a suppressed PTH level. Conclusion The impact of an intervention on clinician evaluation and treatment of patients with hypercalcemia has been previously tested and shown to be beneficial. In this study, the method of directly sending a letter to patients yielded clinically significant results, with 20 patients out of 396 (5.1%) having a PTH level tested. A majority had an overt or suspected parathyroid disease, and out of them, 11 underwent referral for treatment.

Impact of serum vitamin D level on selected bone-related markers in obese- type 2 diabetes patients

Background: Type 2 diabetes mellitus (T2DM) is accompanied by an increased risk for skeletal fractures. The causes are probably a mix of factors, including poor glycemic control, a higher risk of falling due to hypoglycemia, osteopenia, bone quality deterioration, and drug side effects related to bone fragility. Undercarboxylated osteocalcin (ucOC) is a protein generated by osteoblasts that affects insulin secretion and sensitivity. Methods: A total number of 47 obese (BMI ˃ 30) patients with confirmed type 2 diabetes were selected depending on the American Diabetes Association ADA criteria. The control participants were similar to the patients in age and gender, with a total number of 43 obese (BMI ˃ 30) and healthy subjects chosen from the general population. The selected subjects were grouped according to their serum vitamin D levels. Their blood specimen was used for assaying ucOC, parathyroid hormone (PTH), and vitamin D3 levels by specific ELISA kits, and to estimate calcium (Ca2+) levels and inorganic phosphate (PO43−) via enzymatic colorimetric methods. Results: Serum parathyroid hormone and inorganic phosphate median (IQR) values were markedly increased in patients with T2DM when compared to healthy controls, whereas serum calcium and ucOC levels were lowered significantly in diabetic patients when compared to healthy controls. This was irrespective of serum vitamin D levels. Conclusions: Elevated serum levels of PTH and PO43− values in obese type 2 diabetic patients compared to obese non-diabetic controls were accompanied by a significant decrease in ucOC and Ca2+ levels, irrespective of serum vitamin D levels. Hence, serum vitamin D3 levels had no significant impact on levels of ucOC, PTH, Ca2+, and PO43− in obese patients with type 2 diabetes.

Pathology of the Gastrointestinal Tract in Patients with Primary Hyperparathyroidism

Aim. To present data of Russian and foreign studies on the prevalence, pathogenesis and clinical picture of gastrointestinal tract (GIT) pathology in patients with primary hyperparathyroidism (PHPT).Key point. At the beginning of the 20th century PHPT was considered a severe endocrine disease with specific bone and kidney complications, however in 1957 W.T. St Goar proposed a mnemonic triad to recognize this pathology as “diseases of stones, bones and abdominal groans”. A high frequency of gastrointestinal complaints, peptic ulcer, pancreatitis, cholelithiasis in patients with PHPT has been reported. Hyperparathyroidism has been shown to cause smooth muscle atony with specific upper and lower GI symptoms such as nausea, heartburn and constipation. The prevalence of peptic ulcer in patients with PHPT, according to studies of the 50s–60s of the last century, ranged from 10 to 25 %. However, studies linking PHPT to peptic ulcer development were performed before the advent of proton 1). On the other hand, the development of pancreatitis in PHPT is one of the most studied pathologies. In developing countries its frequency can reach 10–20 % due to the absence of routine screening for blood calcium. Some authors report the impact of elevated parathyroid hormone levels on the formation of gallbladder stones by inhibiting of gallbladder emptying, hepatic bile secretion and mobility of the sphincter Oddi, and changing of the bile composition. A number of studies have found an increased risk of developing malignant neoplasms of the intestine, especially the colon, in patients with PHPT.Conclusion. The digestive manifestations of parathyroid dysfunction in patients can often be overlooked, and serum calcium levels should be included in the routine examination in the presence of abdominal symptoms.

BIOCHEMICAL WITH NORMAL PARATHYROID HORMONE : A CASE REPORT

Normo-hormonal primary hyperparathyroidism(NPHPT) is an uncommon condition which has been increasing in last decade. This milder biochemical entity remains incompletely understood due to lack of long term health outcomes regarding management. NPHPT poses two challenges to the surgeon, rst is when to operate and second is the use of intra-operative parathyroid hormone assay to predict the success of surgery. Here we present a 53 year old lady who came with low back ache of more than 2 years duration. It is found to have elevated calcium levels and on further evaluation found to have high normal parathyroid hormone levels in two occasions. Pre operative localization studies were done by suspecting normo-hormonal hyperparathyroidism which showed concordant lesions in both ultrasound neck and Sestamibi scan. She underwent focused parathyroidectomy with intra-operative parathyroid hormone levels which dropped in to less than 30pg/ml. Postoperative calcium was within normal limits and she was symptomatically better. In patients with symptoms of hypercalcemia, elevated calcium levels and high normal intact parathyroid hormone levels should be considered as inappropriate and should lead to the suspicion of normo-hormonal hyperparathyroidism. Intra operative parathyroid hormone levels below 30pg/ml can be utilized as an indicator of successful operation in normo-hormonal hyperparathyroidism.In symptomatic hypercalcemic patients, even if the parathyroid hormones are high normal, a further investigation should be done to locate the parathyroid adenoma and surgery is the best cure

Mandibular brown tumor revealing an ectopic parathyroid adenoma

The case report presents a 47-year-old female patient. She was suffering a painful clinical mandibular lesion. The histological diagnosis returned in favor of a brown tumor (osteitis fibrosa cystica). The patient did not present any signs of hypercalcemia. The biology report shows an hypercalcemia and an elevated parathyroid hormone (PTH) levels. The Sestamibi (methoxyisobutylisonitrile) scintigraphy returned in favor of an ectopic pathological parathyroid tissue in the upper mediastinal zone. The excision of this tissue revealed a parathyroid adenoma, which normalized the metabolic state and regressed the mandibular lesion. This case study highlights the importance of the dosage of parathyroid hormones and the calcemia in identifying the origin of osteitis fibrosa cystica.

Syndrome similar to Familial Hypocalciuric Hypercalcemia (FHH) produced in mice deleted of the gene encoding transient receptor potential canonical channel 1 (TRPC1)

We recently found that global deletion of TRPC1 produces phenotypes similar to FHH [1]. These TRPC1 null mice have mildly elevated serum Ca in both fasted and unfasted conditions from 3.5 through 21.5 months of age, and inappropriately elevated parathyroid hormone (PTH) levels.

Parathyroid Carcinoma: A Diagnostic Challenge – A Case Report

Introduction Parathyroid carcinoma is a rare endocrine carcinoma, presenting as hypercalcemia with elevated parathyroid hormone (PTH) levels, and with renal and bone involvement. It is often misdiagnosed as parathyroid adenoma, resulting in conservative resection of the parathyroid gland and recurrence or metastasis after a few years. Case Description A 52-year-old, morbidly obese woman presented with asymptomatic hypercalcemia and elevated PTH. Ultrasound of the neck showed a cystic lesion adjacent to the right thyroid lobe. Sestamibi (MIBI) parathyroid scintigraphy showed increased radiopharmaceutical uptake by the right superior parathyroid gland without any enlarged or suspicious lymph nodes. She was diagnosed with primary hyperparathyroidism. She underwent right superior parathyroidectomy and en bloc right thyroid lobectomy due to suspicion of parathyroid carcinoma. The histological examination was consistent with parathyroid carcinoma. Discussion Parathyroid carcinoma is a rare disease with no clear diagnostic criteria. The curative treatment for parathyroid carcinoma is the initial en bloc resection. Therefore, early diagnosis is important and high clinical suspicion is warranted in patients with severe hypercalcemia and markedly elevated PTH, with or without palpable neck mass, and renal or bone involvement.

Advances and Updates in Parathyroid Pathology.

Hyperparathyroidism is a common endocrine disorder characterized by elevated levels of parathyroid hormone and hypercalcemia and is divided into 3 types: primary, secondary, and tertiary. Distinction between these types is accomplished by correlation of clinical, radiologic, and laboratory findings with pathologic features. Primary hyperparathyroidism occurs sporadically in 85% of cases with the remaining cases associated with multiple familial syndromes. The pathologic manifestations of primary hyperparathyroidism include parathyroid adenoma, parathyroid hyperplasia, and parathyroid carcinoma. Recent advances in the understanding of the pathogenesis of parathyroid disease has helped to refine the diagnosis and classification of parathyroid lesions. The identification of multiple clonal proliferations in traditional multiglandular parathyroid hyperplasia has led to the adoption by the World Health Organization (WHO) of the alternate term of primary hyperparathyroidism-related multiglandular parathyroid disease. Additional nomenclature changes include the adoption of the term atypical parathyroid tumor in lieu of atypical parathyroid adenoma to reflect the uncertain malignant potential of these neoplasms. Clinical and morphologic features characteristic of familial disease have been described that can help the practicing pathologist identify underlying familial disease and provide appropriate management. Use of ancillary immunohistochemistry and molecular studies can be helpful in classifying parathyroid neoplasms. Parafibromin has proven useful as a diagnostic and prognostic marker in atypical parathyroid tumors and parathyroid carcinomas. This review provides an update on the diagnosis and classification of parathyroid lesions considering the recent advances in the understanding of the molecular and clinical features of parathyroid disease and highlights the use of ancillary studies (immunohistochemical, and molecular) to refine the diagnosis of parathyroid lesions.

PSAT212 Hyperparathyroidism Secondary to Ectopic Parathyroid Adenoma

Abstract Background In the majority of cases, primary hyperparathyroidism is caused by a parathyroid adenoma, most commonly located within the parathyroid glands. However, in some cases, the parathyroid adenoma can be located aberrantly. Clinical case A 78 year old female was referred due to hypercalcemia (ionized calcium 1.63mmol/L). Patient has been known to have elevated calcium (both total and ionized) levels for 3 years and osteoporosis. Initial work up on presentation had been unremarkable hence no further investigation was done and treatment was given. Prior to consult, patient had symptoms of bone pains, particularly in her lower extremities. Kidney function was normal. Patient had never had kidney stones but x-ray demonstrated compression fracture of L2 vertebrae. Work up for hypercalcemia was done, revealing the following results: PTH 196.60 pg/mL, TSH 1.810 mIU/mL, FT4 16.46 pmol/L, FT3 3.55 pmol/L, 24 hour urine calcium 88.40 mg/24 hours, and 25 (OH) D 18.32 ng/dL. Neck ultrasound showed findings of normal-sized thyroid gland with mild parenchymal change, benign cystic nodules and no definite evidence of parathyroid nodule. Parathyroid subtraction imaging was done and demonstrated no scintigraphic evidence of parathyroid adenoma or hyperplasia. Patient was prescribed with calcimimetics (Cinacalcet). However, the patient experienced nausea and body pains and opted to discontinue the medication. Further investigation was performed. Radionucleotide parathyroid imaging using Technitium-99m sestamibi was done which revealed slightly increased tracer activity in the lower midline neck on SPECT imaging, an atypical scintigraphic finding of an aberrantly located parathyroid adenoma possibly in the tracheoesophageal or retroesophageal region. There was no definite scintigtaphic evidence of parathyroid adenoma or hyperplasia in the thyroidal beds or ectopic parathyroid in the mediastinum. A second parathyroid scan with SPECT-CT was performed in another institution and showed a 1.2×1.0 cm, sestamibi avid nodule inseparable from the esophagus and left posterior aspect, anterior to the T2 vertebra, consistent with a thoracic retro-esophageal hyperfunctioning parathyroid adenoma. Patient refused surgery at this point and was given medical management with hydration, Vitamin D correction and antiresorptive agent. Conclusion Multiple imaging may be needed to reach an accurate diagnosis for persistent hypercalcemia and elevated parathyroid hormone levels with an absence of lesions in the neck. If the criteria for surgery are met, as with parathyroid adenomas within the parathyroid gland, surgical resection is also the gold standard of therapy for ectopic parathyroid adenomas. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT217 Estrogen Deficiency as a Cause of Decreased 1- alpha - hydroxylase Activity

Abstract Case description A 40 year old woman receiving cholecalciferol therapy -10,000 IU, and alfacalcidol 1 mcg per day showed a 25 (OH) D increase to 351. 1 ng/mL (normal 65-100) with a normally high parathormone level of 33.5 pg/mL (normal 15-65). Clinically, symptoms of vitamin D deficiency - decreased immunity, decreased muscle mass and strength, depression, and symptoms of estrogen deficiency (hot flashes, scanty menstruation, hair loss) persisted against a high 25(OH)D background, so estrogen determination was performed in the steroid profile of saliva. Estradiol content was decreased - 3.45 pg/ml (norm 4.17 - 9.28), in connection with which transdermal estrogen therapy in a dose of 3.0 g was prescribed. Against the background of estrogen therapy, parathormone decreased from 33.5 to 22.4 pg/ml. Determination of 25(OH)D and estradiol in saliva was performed by mass spectrometry, determination of parathormone by ELISA. Discussion Vitamin D status depends on several factors, in particular on the activity of the enzyme 1 - alpha-hydroxylase (CYP27B1) in the kidney, which converts 25 (OH) D into the active form (1,25 - (OH)2 - D), which in turn depends on both parathormone and sex steroids (estrogen and androgens), determination of which is not a routine practice in vitamin D deficient patients. Elevated parathormone levels are considered a marker of vitamin D deficiency (secondary hyperparathyroidism). Decreased parathormone levels are considered a laboratory manifestation of vitamin D overdose. In this patient, there was no decrease in parathormone below the differential level of 25(OH)D in the background of high levels. Sex steroids increase the synthesis of calcitriol (D hormone, dihydrocholecalciferol 1,25 - (OH)2 - D) by activating the enzyme 1 - alpha - hydroxylase (CYP27B1) in the kidneys. In particular, estradiol deficiency exacerbates vitamin D deficiency. Conclusion Determination of 25(OH)D levels in patients with decreased 1 -alpha-hydroxylase activity leads to hypodiagnosis of vitamin D deficiency. In all patients with high 25(OH)D levels, the determination of parathormone as well as estrogens in saliva is necessary. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP117 Pseudohypoparathyroidism Type IB: A Rare Cause of Hypocalcemia

Abstract Introduction Pseudohypoparathyroidism (PHP) describes disorders of hypoparathyroidism that are the result of resistance of target tissues to the actions of parathyroid hormone (PTH). Studies have estimated the prevalence of PHP to be 0.34 in 100,000 in Japan and 1.1 in 100,000 in Denmark. The first biochemical abnormalities to become apparent are elevated serum levels of PTH and elevated serum levels of phosphorus, followed by hypocalcaemia. We present a patient diagnosed with PHP Type 1B (PHP1B), which was presented to us many years after her initial diagnosis, with other major comorbidities now present. Case description This patient is an 81 year old female presenting to the clinic to discuss her previously diagnosed PHP1B. Her past medical history revealed she began having symptoms of intermittent muscle cramping at the age of 22, followed by carpopedal spasms and periorbital paresthesia a year later. She has also had a physical examination significant for a positive Trousseau sign, but no phenotypical signs of Albright hereditary Osteodystrophy (AHO). Lab evidence from 1977 was recovered showing urinary cyclic AMP level <20 nmol/mg after administration of PTH, consistent with PHP1B. The family history in her parents and children has revealed no similar genetic history so far. Other comorbidities she has developed since her diagnosis are hypokalemia, hypothyroidism, osteoporosis with a femur fracture, obesity, chronic kidney disease and nephrolithiasis. She has been continuing treatment throughout her life with calcium, calcitriol and vitamin D supplementation for hypocalcemia. She has been mostly eucalcemic since then, and complains of occasional carpopedal spasms and perioral numbness. Discussion PHP1B is isolated resistance to PTH in the kidney and normal PTH response in bone without features of AHO. PHP1A and 1C have PTH resistance in bone, and both express AHO. These various forms of PHP are due to defects in the GNAS gene that lead to decreased expression of the alpha-subunit of G protein (Gsa). In the absence of molecular analysis, the clinical and biochemical overlap between PHP and related disorders can lead to challenges in diagnostic classification. There are 2 types of PHP1B cases- autosomal dominant (AD) and sporadic. However, the majority of Patients with PHP1B do not have mutations within the GNAS but they have methylation and imprinting defects that result in absence of maternal Gsa. To emphasize, epimutation study rather than sequencing of the coding region in GNAS should be performed for genetic investigation, which has now become standard practice. Although there is no difference in clinical presentation between AD PHP1B and sporadic PHP1B, their differentiation early during the disease onset can help providers give patients more reliable genetic and reproductive counseling and provide optimal medical management of complications such as hypocalcemia. Presentation: No date and time listed

ODP102 Indicators for the effects of calcimimetics on hypercalcemia in the elderly patients with primary hyperparathyroidism.

Abstract Primary hyperparathyroidism (PHPT) is the most common disorder causing hypercalcemia, in which parathyroid hormone (PTH) is excessively secreted from a parathyroid tumor. PHPT occurs mainly in elderly women, and patient with PHPT present symptoms including nephrolithiasis, bone fracture, and cognitive impairment or can be asymptomatic. Excessive secretion of PTH leads to elevated serum levels of alkaline phosphatase as well as calcium and decreased serum inorganic phosphate level. Parathyroid surgery is the only established treatment, and the treatment reduces elevated serum levels of calcium and PTH, increases bone mineral density, reduces the occurrence of bone fractures, and decreases the risk of renal stones. However, some PHPT patients, especially elderly patients, refuse to undergo surgical therapy for various reasons including perceived risk. Calcimimetic treatment, including cinacalcet and evocalcet administration, has also been reported to be effective for reducing serum calcium level in patients with PHPT. However, the relationship between the efficacy of calcimimetic treatment for PHPT and patient characteristics related to the effectiveness of calcimimetics remains to be elucidated. To investigate the relevance of clinical parameters to the effectiveness of calcimimetics for PHPT, we retrospectively analyzed patients with PHPT who received calcimimetic treatment in our department. We included nine patients including 8 females (88.9%) and one male (11.1%) in the study. The median age of the patients was 81 years (interquartile range (IQR): 61-86 years). Laboratory tests before calcimimetic treatment revealed that median level of serum corrected calcium (cCa) was high (11.1 (IQR: 10.5-12.7) mg/dL), serum inorganic phosphate was low (2.3 (2.3-2.4) mg/dL), and plasma intact PTH was high (251. 0 (198.3-498.5) pg/mL). The fractional excretion of calcium was higher than 1% (1.3% (1.12-1.48%)), %tubular reabsorption of phosphate was low (79.9% (77.1-83.9%)), nephrogenous cyclic adenosine monophosphate (cAMP) was high (3.4 (2.4-4. 0) nmoL/dL GF), and urinary cAMP was normal (4.3 (4. 0-5.3) μmoL/day). Median reduction rate of serum cCa level due to calcimimetic treatment was 5.8% (0-13.4%) at the first follow-up (median treatment duration: 22 (20-29) days). Notably, reduction rate of serum cCa level had significant correlations with age (R=0.95), dual energy X-ray absorptiometry % young adult mean (DEXA %YAM) in the femoral neck (R=-0.92), and urinary cAMP level (R=-0.85). Thus, the present study suggested that elevated serum cCa levels may be reduced by treatment with calcimimetics more effectively in PHPT patients of relatively advanced age, patients with low DEXA %YAM, and patients with low urinary cAMP. Presentation: No date and time listed

LBSAT229 Extended-release Calcifediol Effectively Raised 25-hydroxyvitamin D In CKD Despite Obesity

Abstract Inadequate levels of serum total 25-hydroxyvitamin D (25D) in chronic kidney disease (CKD) are associated with an increased risk of secondary hyperparathyroidism (SHPT). Serum 25D can be difficult to raise sufficiently with vitamin D supplements (cholecalciferol or ergocalciferol) to effectively lower elevated parathyroid hormone (PTH) levels especially in overweight patients. Obesity is common in CKD and requires attention when vitamin D repletion is considered. Vitamin D supplements are fat-soluble molecules which accumulate in adipose tissue. They have low affinity for serum vitamin D binding protein and are poorly mobilized from adipose tissue into circulation for hepatic activation. Recent studies suggest that serum 25D levels of ≥50 ng/mL are necessary to produce significant PTH reductions in nondialysis patients. Data were analyzed from two identical randomized clinical trials investigating the efficacy and safety of treating adult nondialysis patients with extended-release calcifediol (ERC; n=285) or placebo (n=144) to see if ERC raised 25D to at least 50 ng/mL in all body weight categories, with subgroup analyses by race, gender and age. On enrollment, subjects had eGFR of ≥15 and <60 mL/min/1.73 m2, PTH ≥85 and <500 pg/mL, serum 25D ≥10 and <30 ng/mL, corrected serum calcium ≥8.4 and <9.8, serum phosphorus ≥2. 0 and <5. 0, absence of nephrotic range proteinuria (>3 mg/mg creatinine) and no history of parathyroidectomy or renal transplantation. These subjects had mean (SD) age of 65.4 (10.9) years, serum 25D at baseline of 19.6 (5.4) ng/mL, body weight of 97.8 (24.3) kg and BMI of 34.7 (7.9) kg/m2. Fifty percent were male, 64. 0% White, 32.9% African-American or Black, and 3.1% Other, and 20% were Hispanic. A total of 356 subjects completed a 20- to 26-week treatment period per-protocol and were included in the analysis. Enrolled subjects ingested a 30 mcg capsule of ERC (OPKO Pharmaceuticals, Miami) daily for 12 weeks followed by one or two capsules (30 or 60 mcg) daily for a 14 more weeks. Control subjects received matching placebo. Mean (SD) serum 25D remained unchanged with placebo treatment but rose progressively with ERC treatment to 67.1 (21.6) ng/mL (mean of weeks 20-26). The observed increases in serum 25D were inversely related to body weight but exceeded 50 ng/mL in all body weight categories, irrespective of race (White vs. African-American or black), gender or age (<70 vs. ≥70 years). Side effects observed at these levels were similar to placebo. These data showed that ERC successfully raised mean serum 25D to at least 50 ng/mL irrespective of body weight, race, gender or age. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Late Recurrence of Hyperparathyroidism: Parathyromatosis or Recurrent Parathyroid Carcinoma?

A middle-aged woman presented with elevated calcium (10.7 mg/dL [0.28 mmol/L]) and parathyroid hormone (131 pg/mL [4,663.6 pmol/L]) levels. A sestamibi scan exhibited a right upper parathyroid lesion. Parathyroidectomy revealed a 3152 mg right upper parathyroid gland and the intraoperative parathyroid hormone level decreased by 90% (from 27.1 to 2.6 pmol/L; reference range, 1.3-6.8 pmol/L). The lesion was removed intact without any “spillage.” Histology revealed hypercellular parathyroid with intravascular tumor clusters at the periphery of the main lesion.

ODP561 Unilateral Vestibular Schwannoma as the Presentation and Aggravation to be Severe Primary Hyperparathyroidism

Abstract Background A rare benign and slow-growing tumor as vestibular schwannoma (acoustic neuroma) usually presents with asymptomatic/unilateral hearing loss or tinnitus and loss of balance between the ages of 49 to 60 years. 90% of vestibular schwannoma are unilateral and not specifically grown in patients with neurofibromatosis type2 (NF2) (1). The association of schwannoma and parathyroid adenoma has been published not much but consistently until now. However, those were not mention to the relationship between pre- and post-treatment of schwannoma with parathyroid hormone level. Clinical case: A 65-year-old woman, previously healthy, presented with progressive fatigue and loss of balance for 1 month. She developed hearing loss, dysarthria and facial palsy within 1 week. At her first visited, she looked drowsiness and had slow verbal and motor response with right facial palsy, lower motor neuron type. She lost only her right facial sensation by pinprick and hyperreflexia without significant other neurological deficits and abnormal skin lesions. She denied family history of NF2. Severe hypercalcemia (17.66 mg/dL) with markedly elevated parathyroid hormone (PTH 1,115.1 pg/mL; 15-68.3) levels and mild elevation of serum creatine (Cr 1.32 mg/dL) was revealed. MRI brain showed an extra-axial enhancing mass at right CPA-IAC region size 3.7×4.2×2.9 cm possible vestibular schwannoma, this mass causing pressure effect to right sided of pons, medulla, cerebellar hemisphere and fourth ventricle. After treatment with saline hydration, her serum creatinine was recovered to normal range with slightly high normal serum calcium (11.85 mg/dL) but not being well. She came back to hospital again with fatigue and polyuria for 3 days. Her serum calcium rose up to 21.3 mg/dL with very high PTH level; 1,643 pg/mL and elevation of serum creatine (Cr 1.71 mg/dL). Again, she was treated with saline hydration for 3 days before receiving zoledronate 4 mg intravenously. After that her serum calcium and creatinine returned to normal level (Ca 10.32 mg/dL, Cr 1. 08 mg/dL) with being better. She was undergone surgery for removal right vestibular tumor and proved to be schwannoma in pathology. During further investigation of hyperparathyroidism, she had normocalcemia and her PTH level dropped to about 400 pg/mL. Conclusion Our patient showed the contribution of vestibular schwannoma to rise up the level of PTH as same level as parathyroid carcinoma. There could be some relationships of mechanism between there two diseases that should be explored further. Reference: 1. Carlson ML, Link MJ. Vestibular Schwannomas. Review article. N Engl J Med 384;14,Apr 8, 2021. Presentation: No date and time listed

ODP109 PARATHYROID HORMONE AND 25 OH VITAMINA D IN PREGNANCY: DATA FROM AN ARGENTINEAN COHORT SUPPORTING SUPPLEMENTATION.

Abstract Vitamin D (Vit D) deficiency has become a global health care issue, as it affects a great number of women during pregnancy and lactation. Vit D levels are critical during pregnancy, being the mother the only source of them for the developing fetus; an enzymatic system for conversion of 25OH VitD into 1-25(OH) 2 VitD is present in the placenta, thus reinforcing the importance of VitD during gestation. VitD deficiency has been associated with obstetric complications and adverse outcomes in offspring, affecting skeletal, immunological and respiratory systems. It is known that prenatal supplements available do not contain enough VitD to fulfil requirements. It is generally accepted that elevated PTH is an indicator of VitD deficiency, and Hysaj O et al (2021) showed that 25OH VitD is a statistically significant determinant of PTH levels in early and late pregnancy. Aim To evaluateVitD status and its relationship to parathyroid hormone (PTH) in a cohort of pregnant women representative of multiple Argentinian regions. Subjects and Methods Data from samples of 423 pregnant women in 1st and 2nd trimester were collected between 2016 and 2021. VitD was measured in different platforms: DiaSorin Liaison CLIA (n=184), Roche COBAS ECLIA (n=166), Abbott ARCHITECT CMIA (n=33), Biomérieux VIDAS ELFA (n=18) and Siemens CENTAUR CLIA (n=16). PTH (ng/L) was measured in 162 samples by SIEMENS IMMULITE CLIA and Roche COBAS ECLIA. As VitD is light-exposure dependent, we considered warm and high light-exposure season period from December to March and cold and low light season from April to September. VITD (ng/L) levels were classified as Deficient (<20), Insufficient (between 21 and 29) and Sufficient (>30) (Endocrine Society, 2014). Results From 423 data collected, 102 were excluded because of lacking information on VitD supplementation. From the remaining non supplemented 321 samples, 48% resulted insufficient, 30% deficient and 22% sufficient for VitD (groups comparison: p< 0. 05, Kruskal Wallis-Dunn test). The seasonal period and pregnancy trimester distributions didn't show significant differences. Similar results of VitD insufficiency were found in the major used platforms, regardless the seasonal period considered. PTH results expressed as median and interquartile range were (ng/L): 32. 0 (13.7-169. 0) in Deficient pregnancies (N=92), 23.7(13.3-88. 0) in Insufficient (n=50) and 18.7 (9.8-55.7) in Sufficient (n=20). Conclusions This study shows VitD inadequate levels in 78% in non-supplemented pregnancies, regardless season or measurement platform. Relative elevated levels of PTH were associated to pregnancies with VitD deficiency, evidenciating a regulatory role according to published data. To improve VitD status during pregnancy it would be advisable to pose new strategies for prenatal supplements developed by a multidisciplinary professional team. Presentation: No date and time listed

ODP071 A Fit of Hypophosphatemia

Abstract Background Hypophosphatemia is a commonly encountered electrolyte disturbance that is seen in association with a broad range of disorders. Severe hypophosphatemia can be life threatening and is known to cause seizures. Clinical case: A 65 year old female was found down at home by emergency medical services. She was noted to be frothing and had irregular breathing. She was still confused when she was brought to the emergency department but had no focal neurological deficits on examination. Her mentation subsequently improved without intervention. Her past history was notable for a left parafalcine meningioma which was resected in 2019. Her vital signs were stable at presentation. Laboratory evaluation showed critically low phosphate (0.6 mg/dL, n: 2.5-4.5 mg/dL); other electrolytes including sodium, potassium, calcium and magnesium levels were all normal. Additional work up showed slightly elevated parathyroid hormone level (86.8 pg/mL, n: 15-65 pg/mL), borderline low vitamin D (29.5 ng/mL, n: 30-80 ng/mL) and elevated lactate (2.9 mmol/L, n: 0.5-2.2 mmol/L). The patient was immediately treated with 45 mmol of IV sodium phosphate. Repeat serum phosphate showed rapid normalization and the patient was ultimately discharged without any phosphate supplements. Repeat serum phosphate three months later was normal. Conclusion Although severe hypophosphatemia is known to precipitate seizures, seizure activity itself can induce transient hypophosphatemia. In fact, hypophosphatemia has been proposed as a means to diagnose convulsive seizures and distinguish them from syncopal episodes. Transcellular shift has been proposed as a mechanism to explain this phenomenon. In this case, we believe the patient developed seizures as a sequela of brain surgery and that hypophosphatemia developed as an epiphenomenon. Rapid resolution of hypophosphatemia after cessation of seizures and absence of a credible alternative cause should alert physicians to the possibility of this effect. Presentation: No date and time listed

Bone and mineral metabolism in patients with primary aldosteronism: A systematic review and meta-analysis.

Patients with primary aldosteronism (PA) tend to exhibit a high prevalence of osteoporosis (OP) that may vary by whether PA is unilateral or bilateral, and responsive to PA treatment. To explore relationships between bone metabolism, PA subtypes, and treatment outcomes, we performed a systematic review and meta-analysis. The PubMed, Embase, and Cochrane databases were searched for clinical studies related to PA and bone metabolism markers. Articles that met the criteria were screened and included in the systematic review; the data were extracted after evaluating their quality. R software (ver. 2022-02-16, Intel Mac OS X 11.6.4) was used for the meta-analysis. A total of 28 articles were subjected to systematic review, of which 18 were included in the meta-analysis. We found that PA patients evidenced a lower serum calcium level (mean difference [MD] = -0.06 mmol/L, 95% confidence interval [CI]: -0.10 ~ -0.01), a higher urine calcium level (MD = 1.29 mmol/24h, 95% CI: 0.81 ~ 1.78), and a higher serum parathyroid hormone (PTH) level (MD = 2.16 pmol/L, 95% CI: 1.57 ~ 2.75) than did essential hypertension (EH) subjects. After medical treatment or adrenal surgery, PA patients exhibited a markedly increased serum calcium level (MD = -0.08 mmol/L, 95% CI: -0.11 ~ -0.05), a decreased urine calcium level (MD = 1.72 mmol/24h, 95% CI: 1.00 ~ 2.44), a decreased serum PTH level (MD = 2.67 pmol/L, 95% CI: 1.73 ~ 3.62), and an increased serum 25-hydroxyvitamin D (25-OHD) level (MD = -6.32 nmol/L, 95% CI: -11.94 ~ -0.70). The meta-analysis showed that the ser um PTH level of unilateral PA patients was significantly higher than that of bilateral PA patients (MD = 0.93 pmol/L, 95% CI: 0.36 ~ 1.49) and the serum 25-OHD lower than that of bilateral PA patients (MD = -4.68 nmol/L, 95% CI: -7.58 ~ 1.77). There were, however, no significant differences between PA and EH patients of 25-OHD, or BMD of femoral neck and lumbar spine. BMDs of the femoral neck or lumbar spine did not change significantly after treatment. The meta-analytical results were confirmed via sensitivity and subgroup analyses. Excess aldosterone was associated with decreased serum calcium, elevated urinary calcium, and elevated PTH levels; these effects may be enhanced by low serum 25-OHD levels. The risks of OP and fracture might be elevated in PA patients, especially unilateral PA patients, but could be reduced after medical treatment or adrenal surgery. In view, however, of the lack of BMD changes, such hypothesis needs to be tested in further studies.

The 1,24,25(OH)3D3 metabolite in clinical and experimental CKD: Impact of calcitriol treatment

Calcitriol, and other vitamin D receptor activators, remain a primary treatment for elevated parathyroid hormone levels in patients with end stage kidney disease. The objective of this study was to assess the 24-hydroxylation-mediated metabolism of 25(OH)D3 and 1,25(OH)2D3 in rats with experimental kidney disease treated with calcitriol and in a cross-sectional analysis of patients requiring hemodialysis. Methods: Animals were stratified by creatinine into a time control group or calcitriol (20 ng/kg/day) for 3 weeks following CKD induction using a dietary adenine model (0.25% adenine). Hemodialysis patients were recruited and demographic data including calcitriol prescription was obtained by chart review and participant interview. Vitamin D metabolites were assessed using LC-MS/MS. In the rat model, 1,25(OH)2D3 levels increased substantially in calcitriol-treated rats yet there was no increase in its primary metabolite: 1,24,25(OH)2D3. A lower ratio of 1,24,25(OH)2D3:1,25(OH)2D3 (1,25-VMR) was associated with increased calcium levels in calcitriol treated rats. In hemodialysis patients (N = 86), the level of 1,25(OH)2D3 was substantially higher in calcitriol-treated patients yet there was no difference between groups in 1,24,25(OH)3D3, resulting in a marked decrease in the 1,25-VMR in calcitriol treated patients. In hemodialysis patients treated with calcitriol, 1,25(OH)2D3 and a lower ratio between 1,24,25(OH)3D3 and 1,25(OH)2D3 were associated with higher serum calcium levels. Impaired metabolism of exogenous calcitriol may contribute to the adverse effects associated with this treatment. A better understanding of the uniquely dysfunctional catabolic vitamin D profile in CKD may guide more effective treatment strategies.

Normocalcemic non-renal hyperparathyroidism

Parathyroid hormone (PTH) is produced by the parathyroid glands, which are the main regulators of calcium and phosphorus metabolism. Hyperparathyroidism is a clinical condition associated with an increase in serum PTH content. The state of parathyroid glands depends very much on the amount of vitaminD, magnesium and boron in the blood because, according to official data, substantiated by a number of scientific studies, the majority of the world population (80%) has a lack/deficiency of vitamin D. This fact explains the high prevalence of thyroid diseases (hyperplasia, adenoma, hyperparathyroidism) and associated pathology. Previous studies have shown that a deficiency/lack of vitaminD was found in 85–94% of Ukraine population. A deficiency/lack of vitamin D compensatorily stimulates an increase in PTH synthesis. Doctors very rarely determine the level of PTH, which prolongs the progression of hyperparathyroidism, and they detect it only with severe associated changes in other systems. Hyperparathyroidism occurs when one or more of the parathyroid glands become hyperactive, gradually leading to elevated serum parathyroid hormone levels and hypercalcemia. The diagnostic criteria for hyperparathyroid conditions are very vague, which is confusing and leads to unnecessary surgeries instead of simple vitamin D and boron therapy. Normocalcemic primary hyperparathyroidism is a diagnosis of exclusion, and it can be considered only after careful assessment of the causes of secondary hyperparathyroidism, including that associated with a lack of vitamin D. The most common form of hyperparathyroidism is normocalcemic non-renal hyperparathyroidism. Prophylactic use of vitamin D in the correct individualized doses (25(OH)D range of 100–150 nmol/l or 40–60 ng/ml) should reduce the risk of parathyroid pathology but only 10% of the population receives such therapy, others do not know that it is useful. The only way to eliminate the gradual progression of parathyroid disorders is to administer individual prophylactic or therapeutic doses of vitaminD.