SAT-369 Parathyroid Microadenomas as a Cause of Normocalcemic Primary Hyperparathyroidism (PHPT) and a Surgical Challenge

Abstract Background: Patients with normocalcemic primary hyperparathyroidism (PHPT) share similar risks of osteoporosis and nephrolithiasis with patients having hypercalcemic PHPT. The prevalence and natural history of normocalcemic PHPT is not well defined. Parathyroid microadenomas weighing < 100 mg may present as special clinical challenges in both the diagnosis and surgical resection. Clinical Case: A 55-year-old woman presented for an evaluation of osteoporosis following a non-traumatic L1 compression fracture at the age of 50 years. Noting an initial serum calcium of 10 mg/dL, we diagnosed her with normocalcemic PHPT based on a concurrent parathyroid hormone (PTH) level of 112 pg/mL (12-88 pg/mL) and a lack of other causes for an elevated PTH, including a normal eGFR, serum 25-hydroxyvitamin D, 24-hour urine calcium, and autoantibodies for celiac disease. Initial dual-energy x-ray absorptiometry (DXA) scan from 2015 showed normal bone mineral density (BMD) and T-scores in the L-spine, total hip, and femoral neck. Neck imagings, including ultrasound, sestamibi scan, and 4D CT, failed to localize a parathyroid adenoma. In the absence of a target and indications for parathyroidectomy other than osteoporosis, she was treated with bisphosphonates. While her serum calcium remained normal (9.6-10.2 mg/dL) despite an elevated PTH level (92-116 pg/mL) over a two-year period, subsequent DXA scans showed a significant loss in BMD on the bisphosphonates, prompting a peripheral DXA scan, which revealed severe osteoporosis at the distal third of the forearm (BMD 0.450 g/cm2, T-score -3.7), consistent with PTH-associated bone resorption. Following a 4-gland exploration with removal of 2 parathyroid microadenomas (63 and 100 mg), intra- and post-operative PTH levels normalized. She now awaits a repeat DXA scan at 1 year after a successful parathyroidectomy. Conclusion: Although many patients with normocalcemic PHPT may progress to develop hypercalcemia, some remain normocalcemic over an extended period. We report a patient who maintained normocalcemia for over 2 years. To correctly establish the diagnosis of normocalcemic PHPT, a comprehensive evaluation must be performed to exclude secondary causes of an elevated PTH (renal insufficiency, hypovitaminosis D, hypercalciuria, and malabsorption). Since significant osteoporosis may be preferentially seen in the cortical bone, BMD at the distal 1/3 of forearm should be evaluated in addition to the L-spine, hips and femoral necks. When a parathyroid adenoma cannot be localized in patients with normocalcemic PHPT, a careful 4-gland exploration for parathyroid microadenoma(s), paying special attention to the size, texture, and shape of the glands, and guided by intraoperative PTH levels, ensures the successful removal of the culprit gland(s).

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Primary Hyperparathyroidism in Sickle Cell Disease: An Unknown Complication of the Disease in Adulthood

Journal of Clinical Medicine ◽

10.3390/jcm9020308 ◽

2020 ◽

Vol 9 (2) ◽

pp. 308

Author(s):

Elsa Denoix ◽

Charlène Bomahou ◽

Lorraine Clavier ◽

Jean-Antoine Ribeil ◽

François Lionnet ◽

...

Keyword(s):

Sickle Cell Disease ◽

Primary Hyperparathyroidism ◽

Parathyroid Adenoma ◽

Sickle Cell ◽

Serum Calcium ◽

Elevated Serum ◽

Young Patients ◽

Cell Disease ◽

Mineral Density ◽

Cervical Surgery

Primary hyperparathyroidism (pHPT) is the third most common endocrine disorder and usually affects patients between 60 and 70 years of age. To our knowledge, this condition has never been studied in young patients with sickle cell disease (SCD). Our objective was to describe the clinical and biological characteristics of pHPT in adult patients with SCD and its management. We conducted a retrospective study that included SCD patients who were diagnosed with pHPT in four SCD referral centers. pHPT was defined by the presence of elevated serum calcium levels with inappropriate normal or increased parathyroid hormone (PTH) serum levels or histopathological evidence of parathyroid adenoma or hyperplasia. Patients with severe renal impairment (GFR <30 mL/min) were excluded. Twenty-eight patients (18 women, 64%; 22 homozygous genotype, 79%) were included. The median age at pHPT diagnosis was 41 years (interquartile range –IQR- 31.5–49.5). The median serum calcium and PTH concentration were, respectively, 2.62 mmol/L (IQR 2.60–2.78) and 105 pg/mL (IQR 69–137). Bone mineral density (BMD) revealed very low BMD (≤−2.5 SD) in 44% of patients explored (vs. 12.5% among 32 SCD patients matched for SCD genotype, sex, age, and BMI, p = 0.03). Fourteen patients (50%) received surgical treatment, which was successful in all cases, but four of these patients (29%) presented with pHPT recurrence after a median time of 6.5 years. Three of these patients underwent a second cervical surgery that confirmed the presence of a new parathyroid adenoma. These results suggest that SCD is a condition associated with pHPT in young subjects. SCD patients with pHPT have a high risk of very low BMD. A diagnosis of pHPT should be suspected in the presence of mild hypercalcemia or low BMD in SCD patients.

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P114 Effect of vitamin D on parathyroid hormone, serum calcium and bone mineral density in patients with primary hyperparathyroidism being managed conservatively

Rheumatology ◽

10.1093/rheumatology/keab247.110 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Mahrukh Khalid ◽

Vismay Deshani ◽

Khalid Jadoon

Keyword(s):

Bone Mineral Density ◽

Vitamin D ◽

Parathyroid Hormone ◽

Primary Hyperparathyroidism ◽

Bone Mineral ◽

Serum Calcium ◽

Mineral Density ◽

Neck Of Femur ◽

Vitamin D Levels ◽

Significant Difference

Abstract Background/Aims Vitamin D deficiency is associated with more severe presentation of primary hyperparathyroidism (PTHP) with high parathyroid hormone (PTH) levels and reduced bone mineral density (BMD). We analyzed data to determine if vitamin D levels had any impact on PTH, serum calcium and BMD at diagnosis and 3 years, in patients being managed conservatively. Methods Retrospective analysis of patients presenting with PHPT. Based on vitamin D level at diagnosis, patients were divided into two groups; vitamin D sufficient (≥ 50 nmol/L) and vitamin D insufficient (≤ 50 nmol/L). The two groups were compared for age, serum calcium and PTH levels at diagnosis and after mean follow up of 3 years. BMD at forearm and neck of femur (NOF) was only analyzed in the two groups at diagnosis, due to lack of 3 year’s data. Results There were a total of 93 patients, 17 males, mean age 70; range 38-90. Mean vitamin D level was 73.39 nmol/L in sufficient group (n = 42) and 34.48 nmol/L in insufficient group (n = 40), (difference between means -38.91, 95% confidence interval -45.49 to -32.33, p < 0.0001). There was no significant difference in age, serum calcium and PTH at the time of diagnosis. After three years, there was no significant difference in vitamin D levels between the two groups (mean vitamin D 72.17 nmol/L in sufficient group and 61.48 nmol/L in insufficient group). Despite rise in vitamin D level in insufficient group, no significant change was observed in this group in PTH and serum calcium levels. BMD was lower at both sites in vitamin D sufficient group and difference was statistically significant at NOF. Data were analyzed using unpaired t test and presented as mean ± SEM. Conclusion 50% of patients presenting with PHPT were vitamin D insufficient at diagnosis. Vitamin D was adequately replaced so that at 3 years there was no significant difference in vitamin D status in the two groups. Serum calcium and PTH were no different in the two groups at diagnosis and at three years, despite rise in vitamin D levels in the insufficient group. Interestingly, BMD was lower at forearm and neck of femur in those with sufficient vitamin D levels and the difference was statistically significant at neck of femur. Our data show that vitamin D insufficiency does not have any significant impact on PTH and calcium levels and that vitamin D replacement is safe in PHPT and does not impact serum calcium and PTH levels in the short term. Lower BMD in those with adequate vitamin D levels is difficult to explain and needs further research. Disclosure M. Khalid: None. V. Deshani: None. K. Jadoon: None.

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Primary Hyperparathyroidism

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2018-01225 ◽

2018 ◽

Vol 103 (11) ◽

pp. 3993-4004 ◽

Cited By ~ 53

Author(s):

John P Bilezikian

Keyword(s):

Primary Hyperparathyroidism ◽

Serum Calcium ◽

Target Organ ◽

Organ Involvement ◽

Mineral Density ◽

Clinical Phenotypes ◽

New Concepts ◽

Clinical Presentations ◽

Surgical Guidelines ◽

Normal Albumin

Abstract Background Primary hyperparathyroidism (PHPT), the most common cause of hypercalcemia, is most often identified in postmenopausal women. The clinical presentation of PHPT has evolved over the past 40 years to include three distinct clinical phenotypes, each of which has been studied in detail and has led to evolving concepts about target organ involvement, natural history, and management. Methods In the present review, I provide an evidence-based summary of this disorder as it has been studied worldwide, citing key concepts and data that have helped to shape our concepts about this disease. Results PHPT is now recognized to include three clinical phenotypes: overt target organ involvement, mild asymptomatic hypercalcemia, and high PTH levels with persistently normal albumin-corrected and ionized serum calcium values. The factors that determine which of these clinical presentations is more likely to predominate in a given country include the extent to which biochemical screening is used, vitamin D deficiency is present, and whether parathyroid hormone levels are routinely measured in the evaluation of low bone density or frank osteoporosis. Guidelines for parathyroidectomy apply to all three clinical forms of the disease. If surgical guidelines are not met, parathyroidectomy can also be an appropriate option if no medical contraindications are present. If either the serum calcium or bone mineral density is of concern and surgery is not an option, pharmacological approaches are available and effective. Conclusions Advances in our knowledge of PHPT have guided new concepts in diagnosis and management.

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Night Sweats as the Presenting Symptom of Primary Hyperparathyroidism

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.421 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A207-A207

Author(s):

Vanessa Williams ◽

Hadoun Jabri ◽

Michael G Jakoby

Keyword(s):

Primary Hyperparathyroidism ◽

Parathyroid Adenoma ◽

Serum Calcium ◽

Vasomotor Symptoms ◽

Temperature Threshold ◽

Hot Flushes ◽

Parathyroid Surgery ◽

Intact Pth ◽

Patient Reported ◽

Night Sweats

Abstract Background: Approximately 25–40% of patients report night sweats in the previous month during appointments with their primary care clinicians. The differential diagnosis for night sweats is broad, with hyperthyroidism, carcinoid syndrome, pheochromocytoma, medullary thyroid carcinoma, insulinoma, and acromegaly as established endocrine causes. We present a case of primary hyperparathyroidism (PHPT) in which the patient’s chief complaint was night sweats and resolution occurred after parathyroidectomy. Case. A 39-year-old female reported one-year of daily night sweats that required changes of clothes and bedding. She denied excessive daytime sweating, frequent palpitations, tremors, nightmares, rashes, fevers, chills, cough, headaches, dizziness, abdominal pain, diarrhea, disrupted menses, or unintentional weight loss. Vital signs and examination were unremarkable. Hypercalcemia (11.0 mg/dL, 8.6–10.3) was noted and confirmed by additional serum calcium measurements. Intact PTH ranged from 27–33 pg/mL (12–88), and 24 h urine calcium (258 mg) excluded familial hypocalciuric hypercalcemia (FHH). Parathyroid scintigraphy and neck ultrasound identified a left neck mass, and the patient underwent successful resection of a left inferior parathyroid adenoma. Hypercalcemia and night sweats initially resolved after surgery, but the patient returned six weeks later with recurrence of night sweats. Reevaluation was notable for serum calcium 10.4 mg/dL, phosphorus 2.4 mg/dL (2.5–5.0), and intact PTH 104 pg/mL. A right superior parathyroid adenoma was identified on repeat parathyroidectomy, and the patient experienced durable resolution of night sweats and hypercalcemia following her second parathyroid surgery. She was screened for multiple endocrine neoplasia type 1 (MEN1) due to multiple parathyroid tumors, though no known pathogenic menin gene variants were identified. Conclusions: A title/abstract search in PubMed linking “hyperparathyroidism” and “hypercalcemia” to “night sweats,” “sleep hyperhidrosis,” “sweating,” “hot flashes,” “hot flushes,” “diaphoresis” and “vasomotor symptoms” yielded only one relevant case of a postmenopausal woman with hot flushes unresponsive to hormone replacement that resolved after parathyroidectomy for PHPT. Hypercalcemia is known to affect central nervous system function. It is possible that in rare cases hypercalcemia alters function of the medial preoptic area, lowering the temperature threshold above which peripheral vasodilatation and perspiration occur to dissipate heat. The patient’s predisposition to only night sweats is unclear, though unlike the first patient reported with PHPT and sweating, our patient is premenopausal. This case indicates that vasomotor symptoms may occur with PHPT and resolve after successful parathyroid surgery.

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Severe Hypercalcemia due to Primary Hyperparathyroidism with MEN 2A

World Journal of Endocrine Surgery ◽

10.5005/jp-journals-10002-1037 ◽

2010 ◽

Vol 2 (3) ◽

pp. 131-133

Author(s):

Geoffrey B Thompson ◽

Benzon M Dy ◽

Bianca Vazquez ◽

Peter J Tebben ◽

Seema Kumar

Keyword(s):

Primary Hyperparathyroidism ◽

Parathyroid Adenoma ◽

Surgical Management ◽

Clinical Presentation ◽

Clinical Manifestations ◽

Mineral Density ◽

Normal Range ◽

Rare Presentation ◽

Severe Hypercalcemia ◽

Men 2A

ABSTRACT Introduction Severe hypercalcemia due to primary hyperparathyroidism (PHPT) is rare in the setting of MEN 2A. Materials and methods Two patients with MEN 2A and severe hypercalcemia were identified recently. Their clinical presentation, evaluation, surgical management and outcomes are reviewed. Results Two patients with MEN 2A were identified with severe hypercalcemia secondary to a parathyroid adenoma. Calcium levels were elevated to 12.7 mg/dL and 15.1 mg/dL, respectively (normal range = 8.9-10.1 mg/dL). In each case, a single parathyroid adenoma was identified and surgically excised with normalization of parathyroid and calcium levels postoperatively. Clinical manifestations at the time of diagnosis included constipation, polyuria, hypercalciuria, and decreased bone mineral density. Conclusion Severe elevation of serum calcium is a rare presentation of PHPT in MEN2A. The differential diagnosis should include parathyroid adenoma, hyperplasia and parathyroid carcinoma. Early surgical management is essential in the treatment of hyperparathyroidism with severe hypercalcemia to prevent further complications.

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Vitamin D status, seasonal variations, parathyroid adenoma weight and bone mineral density in primary hyperparathyroidism

Clinical Endocrinology ◽

10.1111/j.1365-2265.2005.02371.x ◽

2005 ◽

Vol 63 (5) ◽

pp. 506-513 ◽

Cited By ~ 112

Author(s):

B. Moosgaard ◽

P. Vestergaard ◽

L. Heickendorff ◽

F. Melsen ◽

P. Christiansen ◽

...

Keyword(s):

Bone Mineral Density ◽

Vitamin D ◽

Primary Hyperparathyroidism ◽

Parathyroid Adenoma ◽

Bone Mineral ◽

Seasonal Variations ◽

Vitamin D Status ◽

Mineral Density

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Primary Hyperparathyroidism: Modern Conception and Clinical Observation

The Russian Archives of Internal Medicine ◽

10.20514/2226-6704-2020-10-2-94-101 ◽

2020 ◽

Vol 10 (2) ◽

pp. 94-101

Author(s):

L. M. Farkhutdinova

Keyword(s):

Parathyroid Hormone ◽

Primary Hyperparathyroidism ◽

Parathyroid Adenoma ◽

Clinical Manifestations ◽

Premature Death ◽

Developed Countries ◽

Severe Form ◽

Mineral Density ◽

Target Organs ◽

Increased Risk

The article is devoted to one of the actual medical and social problems — primary hyperparathyroidism, the late diagnosis of which leads to the development of severe complications and an increased risk of premature death. Unlike developed countries, where 80% of cases are represented by mild forms of the disease, in the Russian Federation this indicator does not exceed 30%, while 70% are manifest forms. Widespread awareness of doctors of various specialties in the diagnosis of parathyroid adenoma is necessary for the timely detection of the disease. The article reflects the main stages of the study of the disease, the pathogenesis of the clinical manifestations of primary hyperparathyroidism, the classic symptoms of which are changes in the target organs of the parathyroid hormone — bone tissue, urinary system and gastrointestinal tract, is considered. Bone disorders are the most common manifestation of hyperparathyroidism and are characterized by increased bone metabolism with a progressive decrease in bone mineral density. Typical changes in the kidneys include nephrolithiasis and nephrocalcinosis, causing the formation of renal failure. Gastrointestinal signs of hyperparathyroidism are erosion and ulcers of the stomach and duodenum, prone to bleeding, recurrent pancreatitis. Diagnosis of the disease is based on laboratory results, characterized by elevated levels of calcium and parathyroid hormone in the blood. Visualization of the paradenomas in most cases is provided by ultrasound and scintigraphy. Removal of parathyroid adenoma is the most effective treatment. A clinical case of a severe form of the disease is presented, indicating an urgent need to take measures to solve the problem of primary hyperparathyroidism.

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Normocalcaemic hyperparathyroidism and primary hyperparathyroidism: least significant change for adjusted serum calcium

Acta Endocrinologica ◽

10.1530/eje-20-0634 ◽

2021 ◽

Vol 184 (1) ◽

pp. K7-K10

Author(s):

Marian Schini ◽

Richard Jacques ◽

Eleanor Oakes ◽

Nicola Peel ◽

Jennifer S Walsh ◽

...

Keyword(s):

Bone Mineral Density ◽

Clinical Practice ◽

Primary Hyperparathyroidism ◽

Bone Mineral ◽

Serum Calcium ◽

Calcium Metabolism ◽

Parathyroid Surgery ◽

Mineral Density ◽

Least Significant Change ◽

Significant Change

Introduction The least significant change (LSC) is a term used in individuals in order to evaluate whether one measurement has changed significantly from the previous one. It is widely used when assessing bone mineral density (BMD) scans. To the best of our knowledge, there no such estimate available in the literature for patients with disorders of calcium metabolism. Our aim was to provide an estimate of the least significant change for albumin-adjusted calcium in patients with normocalcaemic hyperparathyroidism (NPHPT) and primary hyperparathyroidism (PHPT). Methods We used the within-subject standard deviatio calculated in a population of NPHPT and PHPT patients and multiplied it by 2.77. Results The LSC for NPHPT and PHPT were found to be 0.25 and 0.24 mmol/L, respectively (1.00 and 0.96 mg/dL). In clinical practice, the value of 0.25 mmol/L could be used. Discussion The least significant change given, could be used in two ways in these patients. First, it gives a range to which values are expected. This can provide some reassurance for the patient and the physician in cases of intermittent hypercalcaemia. Moreover, it can be a marker of whether an individual has an actual significant change of his calcium after parathyroid surgery.

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MON-LB66 Altered Mental Status and Hypercalcemia: A Rare Presentation of Pure Osteolytic Metastatic Prostate Cancer

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.2251 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Ajinkya Kulkarni ◽

Mrunal Kulkarni ◽

Rithikaa Ellangovan ◽

Rajesh Thirumaran

Keyword(s):

Prostate Cancer ◽

Primary Hyperparathyroidism ◽

Parathyroid Adenoma ◽

Mental Status ◽

Serum Calcium ◽

Bone Scan ◽

Rare Case ◽

Osteolytic Metastasis ◽

Prostate Cancers ◽

Osteoblastic Lesions

Abstract Background: We present a rare case of hypercalcemia with the concomitant presence of parathyroid adenoma, secondary hyperparathyroidism due to kidney disease and hypercalcemia of malignancy. Mild hypercalcemia due to primary hyperparathyroidism often precedes the acute, more severe hypercalcemia of malignancy. Prostate cancers are usually known to cause osteoblastic lesions. We present a rare case of prostate cancer with pure osteolytic metastasis. Case: 73 year old male with past history of ESRD on hemodialysis was brought to the ER with change in mental status. Labs showed elevated serum calcium 13.3 mg/dl (8.6-10.2 mg/dl) and creatinine 7.0 mg/dl (0.60-1.30mg/dl). Patient underwent emergent hemodialysis. Additional lab work revealed, elevated phosphorus level of 5.8mg/dl (2.5-5 mg/dl), low vitamin D 25-hydroxy of 22 ng/ml (30-100 ng/ml) and vitamin 1-25 dihydroxy level of 7 ng/ml (20-79 ng/ml). Both PTH 172.6 pg/ml (12-88 pg/ml) and PTHrP 64 pg/ml (14-27 pg/dl) levels were elevated. Parathyroid scan showed increased uptake in left inferior parathyroid gland indicating the presence of a parathyroid adenoma. Serum calcium levels remained persistently elevated despite being continued on dialysis with a low calcium bath and receiving calcium lowering therapy with calcium binding agent- cinacalcet, calcitonin, bisphosphonate. Further work up for refractory hypercalcemia revealed an elevated prostate-specific antigen (PSA) level of 1420 ng/ml (0-3.999 ng/ml). Bone scan showed no evidence of osseous metastasis. CT abdomen & pelvis showed extensive lytic bony metastases, with metastasis to lung and lymph nodes in mesenteric root and in the pelvis. Prostate gland showed asymmetric contour along the left posterolateral zone suspicious for malignancy with extracapsular spread.Biopsy from the left iliac lytic bone lesion was done that showed poorly differentiated metastatic adenocarcinoma, consistent with a prostatic primary. The patient was started on treatment with anti-androgen medication- Bicalutamide and prednisone and was planned to be started on Leuprolide as outpatient. Discussion: Hypercalcemia is uncommon in advanced prostate cancer compared to other malignancies where osteolytic metastasis is more common than osteoblastic metastasis. Incidence of malignancy in patients with primary hyperparathyroidism and vice-versa is high, hence serum PTH and PTHrP should be measured in hypercalcemic patients with malignancy. If PTHrP and PTH are both elevated, it indicates co-existent primary hyperparathyroidism. Prostate cancers are usually known to cause osteoblastic lesions and pure osteolytic metastasis from prostate carcinoma is extremely rare. Radio-nucleotide bone scan preferentially detects osteoblastic metastasis. CT or MRI is indicated to look for osteolytic lesions if suspicion for bone metastasis is high.

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