Hyperparathyroidism Abstracts 4

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Primary Hyperparathyroidism.
(Bandeira and Bilezikian, 2016) Download
Over the past several generations, primary hyperparathyroidism (PHTP) has undergone a change in its clinical presentation in many countries from a symptomatic disease to an asymptomatic one. The reasons for this change in clinical presentation are related to the widespread use of biochemical screening tests, to the measurement of PTH more routinely in the evaluation of metabolic bone disease and to the status of vitamin D sufficiency in the population. Along with recognition of a broader clinical spectrum of disease, including a more recently recognized normocalcemic variant, has come an appreciation that the evaluation of classic target organs that can be affected in PHPT, such as the skeleton and the kidneys, require more advanced imaging technology for complete evaluation. It is clear that even in asymptomatic patients, evidence for microstructural disease in the skeleton and calcifications in the kidneys can be demonstrated often. Potential non-classical manifestations of PHPT related to neurocognition and the cardiovascular system continue to be of interest. As a result of these advances, revised guidelines for the management of asymptomatic PHPT have been recently published to help the clinician determine whether surgery is appropriate or whether a more conservative approach is acceptable.

Ultraviolet irradiation corrects vitamin D deficiency and suppresses secondary hyperparathyroidism in the elderly.
            (Chel et al., 1998) Download
The objective of this study was to compare the effect of ultraviolet radiation (UV) and oral vitamin D3 on the vitamin D status and parathyroid hormone (PTH) concentration in elderly nursing home patients. The design of the study was a randomized clinical trial. The setting was a psychogeriatric nursing home. Subjects included 45 female psychogeriatric patients with a mean age of 85 years. Exclusion criteria were going outdoors more than once a week and the presence of actinic or cancer skin lesions. Intervention was random allocation of UV-B irradiation at half the minimal erythemal dose of the lower back, three times per week during 12 weeks (UV-B), or oral vitamin D3 400 IU/day during 12 weeks (VIT-D), or no treatment (CONTR). Main outcome measures were change in fasting serum levels of vitamin D metabolites at 0, 2, 4, 8, and 12 weeks in the treatment groups, compared with the control group. PTH(1-84) was measured at 0 and 12 weeks. Baseline serum 25-hydroxyvitamin D (25(OH)D) was lower than 30 nmol/l in 95% of the participants. It increased to a median value of around 60 nmol/l after 12 weeks both in the UV-B and VIT-D groups, whereas there was no change in the CONTR group. Serum 1,25-dihydroxyvitamin D increased significantly in the UV-B group. Serum calcium increased significantly in both treatment groups. Serum PTH decreased more than 30% in both treatment groups (p < 0.001), whereas there was no significant change in the control group. Irradiation with UV-B in the very elderly for a few minutes per day leads to adequate improvement of the vitamin D status. It is as effective as oral vitamin D3 in increasing serum 25(OH)D and suppressing secondary hyperparathyroidism.

Restless legs syndrome associated with primary hyperparathyroidism
            (Lim et al., 2005) Download
Restless legs syndrome (RLS) is a poorly understood sleep-related movement disorder which can be primary or associated with other conditions, most commonly iron deficiency, uremia and peripheral nerve disease. We present a case of RLS with an unusual secondary cause: primary hyperparathyroidism with hypercalcemia. This patient experienced complete and sustained relief of RLS symptoms immediately after parathyroidectomy, with normalization of her serum parathyroid hormone (PTH) and calcium levels. Early recognition and treatment of this uncommonly detected underlying cause is important because it is potentially curative in this frequently disabling condition for which usually only symptomatic treatment is available.

Arterial Hypertension, Metabolic Syndrome and Subclinical Cardiovascular Organ Damage in Patients with Asymptomatic Primary Hyperparathyroidism before and after Parathyroidectomy: Preliminary Results.
            (Luigi et al., 2012) Download
Background. Primary hyperparathyroidism (PHPT) is associated with high cardiovascular morbidity, and the role of calcium and parathyroid hormone is still controversial. Objective. To evaluate the prevalence and outcomes of metabolic syndrome, hypertension, and some cardiovascular alterations in asymptomatic PHPT, and specific changes after successful parathyroidectomy. Material and Methods. We examined 30 newly diagnosed PHPT patients (8 males, 22 females; mean age 56 ± 6 yrs), 30 patients with essential hypertension (EH) (9 males, 21 females; mean age 55 ± 4), and 30 normal subjects (NS) (9 males, 21 females: mean age 55 ± 6). All groups underwent evaluation with ambulatory monitoring blood pressure, echocardiography, and color-Doppler artery ultrasonography and were successively revaluated after one year from parathyroidectomy. Results. PHPT patients presented a higher prevalence of metabolic syndrome (38%) with respect to EH (28%). Prevalence of hypertension in PHPT was 81%, and 57% presented altered circadian rhythm of blood pressure, with respect to EH (35%) and NS (15%). PHPT showed an important myocardial and vascular remodelling. During follow-up in PHPT patients, we found significant reduction of prevalence of metabolic syndrome, blood pressure, and "non-dipping phenomenon." Conclusions. Cardiovascular and metabolic alterations should be considered as added parameters in evaluation of patients with asymptomatic PHPT.

High prevalence of metabolic syndrome in a mestizo group of adult patients with primary hyperparathyroidism (PHPT).
            (Mendoza-Zubieta et al., 2015) Download
BACKGROUND:  Primary hyperparathyroidism (PHPT) and metabolic syndrome (MS) have been independently related to cardiovascular morbidities, however this association is still controversial. Mexican population has a high prevalence of metabolic syndrome, however its frequency seems to be even higher than expected in patients with PHPT. METHODS:  We retrospectively reviewed the charts of patients that underwent parathyroidectomy for PHPT in a referral center and used the criteria from the National Cholesterol Educational Program (NCEP)/Adult Treatment Panel III (ATP III) to define MS before surgery. We compared the characteristics between the patients with and without MS. RESULTS:  60 patients were analyzed, 77% were female and 72% had a single parathyroid adenoma. MS was present in 59% of the patients, this group was significantly older (57 vs. 48 years, p = 0.01) and they had lower iPTH (115 vs. 161 ng/ml, p = 0.017). Other parameters did not show differences. CONCLUSIONS:  MS is frequent in our population diagnosed with primary hyperparathyroidism, adverse cardiovascular parameters are common and significant differences in calcium metabolism compared to the non-MS group are present.

Improvement of sleep disturbance and insomnia following parathyroidectomy for primary hyperparathyroidism.
            (Murray et al., 2014) Download
BACKGROUND:  The aim of the present study was to investigate the incidence of sleep disturbance and insomnia in patients with primary hyperparathyroidism (PHPT), and to evaluate the effect of parathyroidectomy. METHODS:  A questionnaire was prospectively administered to adult patients with PHPT who underwent curative parathyroidectomy over an 11-month period. The questionnaire, administered preoperatively and 6 months postoperatively, included the Insomnia Severity Index (ISI) and eight additional questions regarding sleep pattern. Total ISI scores range from 0 to 28, with >7 signifying sleep difficulties and scores >14 indicating clinical insomnia. RESULTS:  Of 197 eligible patients undergoing parathyroidectomy for PHPT, 115 (58.3 %) completed the preoperative and postoperative questionnaires. The mean age was 60.0 ± 1.2 years and 80.0 % were women. Preoperatively, 72 patients (62.6 %) had sleep difficulties, and 29 patients (25.2 %) met the criteria for clinical insomnia. Clinicopathologic variables were not predictive of clinical insomnia. There was a significant reduction in mean ISI score after parathyroidectomy (10.3 ± 0.6 vs 6.2 ± 0.5, p < 0.0001). Postoperatively, 79 patients (68.7 %) had an improved ISI score. Of the 29 patients with preoperative clinical insomnia, 21 (72.4 %) had resolution after parathyroidectomy. Preoperative insomnia patients had an increase in total hours slept after parathyroidectomy (5.4 ± 0.3 vs 6.1 ± 0.3 h, p = 0.02), whereas both insomnia patients and non-insomnia patients had a decrease in the number of awakenings (3.7 ± 0.4 vs 1.9 ± 0.2 times, p = 0.0001). CONCLUSIONS:  Sleep disturbances and insomnia are common in patients with PHPT, and the majority of patients will improve after curative parathyroidectomy.

Correction of 25-OH-vitamin D deficiency improves control of secondary hyperparathyroidism and reduces the inflammation in stable haemodialysis patients.
            (Ojeda López et al., 2017) Download
INTRODUCTION:  Patients on haemodialysis (HD) have a high prevalence of 25-OH-vitamin D (25-OH-D)deficiency. Secondary hyperparathyroidismis a common condition in these patients, which is very important to control. 25-OH-D is involved in regulating calcium homeostasis. As such, appropriate levels of this vitamin could help to control bone mineral metabolism. OBJECTIVE:  To evaluate the effect 25-OH-D repletion in HD patients with 25-OH-D deficiency (<20ng/ml) on the control of secondary hyperparathyroidism and microinflammation status. PATIENTS AND METHODS:  Prospective observational study in which stable patients on HD with 25-OH-D deficiency (<20ng/ml) were treated with oral calcifediol 0.266mcg/every 2 weeks for three months. Dialysis characteristics, biochemical parameters and drug doses administered were analysed before and after the correction of the deficiency. RESULTS:  Forty-five stable HD patients with a mean age of 74.08±12.49 years completed treatment. Twenty-seven patients (60%) achieved 25-OH-D levels above 20ng/ml (23 with levels>30ng/ml and 4 between 20-30ng/ml). Parathyroid hormone levels decreased in 32 of the 45 patients, 23 of which (51%) achieved a>30% decrease from baseline. In terms of concomitant treatment, we observed a significant reduction in the selective vitamin D receptor activator dose, but no changes in calcimimetic or phosphate binders administration. In terms of malnutrition-inflammation status, a decrease in C-reactive protein was noted, although other microinflammation parameters, such as activated monocytes (CD14+/CD16+ and CD 14++/CD16+) were unchanged. No changes were observed in the levels of FGF-23. CONCLUSIONS:  Correcting 25-OH-D deficiency in HD patients is associated with better secondary hyperparathyroidism control with lower doses of vitamin D analogues, as well as an improvement in inflammatory status. Our results support the recommendation to determine 25-OH-D levels and correct its deficiency in these patients.


 

Asymptomatic hyperparathyroidism: a medical misnomer
            (Perrier, 2005) Download
Whereas the classic and time-honored manifestations of ‘‘bones, stones, abdominal moans, and psychic groans’’ are not typical of the modern presentation of the disease, most reports suggest that many patients with PHPT discovered in the course of routine biochemical screening may have symptoms that are both vague and extremely nonspecific. At present in the United States, more than 80% of patients with PHPT in fact present with a myriad of nonclassical, subclinical signs and symptoms of this disease. These patients are identified as those whose disease process has yet not evolved to a severe degree but who still exhibit subjective, identifiable symptoms believed to be typical of PHPT.

Neurocognitive dysfunction: a predictor of parathyroid hyperplasia.
            (Repplinger et al., 2009) Download
BACKGROUND:  To determine whether a symptomatic presentation was associated with parathyroid hyperplasia, we retrospectively examined pre-operative symptom profiles of patients who underwent parathyroidectomy. METHODS:  From October 2007 to July 2008, 111 patients with primary hyperparathyroidism completed a preoperative symptom questionnaire prior to parathyroidectomy. The symptom profiles of patients with and without hyperplasia were compared. RESULTS:  Neurocognitive symptoms occurred in 51.4% of patients. Patients with 1 neurocognitive symptom had a 25% risk of parathyroid hyperplasia. Additional neurocognitive symptoms increased the risk of hyperplasia linearly, with hyperplasia occurring in 38% of patients reporting 2 neurocognitive symptoms (P < .001) and 61% of patients reporting 3 or more of these symptoms (P < .001). A negative sestamibi scan was associated with a 33% risk of hyperplasia. Coupled with at least 1 neurocognitive symptom, the risk of hyperplasia was 53.3% (P < .001). Of patients with 3 or more neurocognitive symptoms and a negative localizing scan, 100% were found to have parathyroid hyperplasia (P < .001). CONCLUSION:  The presence of neurocognitive dysfunction in a patient with hyperparathyroidism may be used as a predictor of hyperplastic disease. Three or more of these symptoms, coupled with a negative sestamibi scan, was 100% predictive of parathyroid hyperplasia in our cohort.

Primary hyperparathyroidism.
            (Suliburk and Perrier, 2007) Download
Primary hyperparathyroidism (PHPT) is classically thought of as the somatic manifestation of hypercalcemia in which patients suffer from a variety of complaints including abdominal pain, nephrolithiasis, osteopenia, and mental status changes. Contemporary PHPT patients are generally free of somatic manifestations and are most often diagnosed when routine biochemical testing shows an elevated serum calcium level. The modern day patient may present with much more subtle neurocognitive symptoms including fatigue, lethargy, muscle weakness, depression, and cognitive impairment. Advances in imaging technology, intraoperative parathyroid hormone measurement, and surgical technique now allow parathyroidectomy to be performed using a focused approach without the absolute need of a four-gland exploration. Minimally invasive techniques allow the procedure to be accomplished under local anesthesia on an outpatient basis. This brief review summarizes the presentation, biochemical evaluation, operative intervention, and follow-up care of the modern day PHPT patient.

Does impotence improve after parathyroidectomy in men with primary hyperparathyroidism
            (Yoo et al., 2016) Download
BACKGROUND:  Erectile dysfunction (ED) is a common diagnosis associated with age, hypertension, cardiovascular disease, and diabetes. Primary hyperparathyroidism (PHP) is also seen with these comorbidities, but its association with ED has yet to be studied. We evaluated the rate and resolution of impotence after curative surgery for PHP. METHODS:  Prospectively collected data, including a self-reported questionnaire of symptoms, were reviewed for men who had curative parathyroid exploration for sporadic PHP from July 2010 to January 2014. Data were compared with an age-matched cohort of men who had thyroidectomy during the same period. RESULTS:  Among 160 men with PHP and mean age of 60 years (range, 19-88), preoperative ED was reported by 13%, and this group was older than patients without ED (mean age, 70 vs 58 years, P < .01). Self-reported resolution of ED after parathyroidectomy occurred in 67% compared with 43% of patients in a thyroidectomy cohort. Preoperative mean arterial blood pressure was less in men with postoperative resolution of ED (96.6 vs 105.4 mm Hg, P = .03). Among 3 of 21 men on specific ED medications, 2 no longer required them postoperatively. CONCLUSION:  Impotence is reported often by men undergoing parathyroidectomy for PHP. After curative surgery, 67% of those affected may self-report ED resolution, which may be more pronounced in those patients with a lesser preoperative mean arterial blood pressure.

 


References

Bandeira, L and J Bilezikian (2016), ‘Primary Hyperparathyroidism.’, F1000Res, 5 PubMed: 27508075
Chel, VG, et al. (1998), ‘Ultraviolet irradiation corrects vitamin D deficiency and suppresses secondary hyperparathyroidism in the elderly.’, J Bone Miner Res, 13 (8), 1238-42. PubMed: 9718191
Lim, L. L., et al. (2005), ‘Restless legs syndrome associated with primary hyperparathyroidism’, Sleep Med, 6 (3), 283-85. PubMed: 15854861
Luigi, P, et al. (2012), ‘Arterial Hypertension, Metabolic Syndrome and Subclinical Cardiovascular Organ Damage in Patients with Asymptomatic Primary Hyperparathyroidism before and after Parathyroidectomy: Preliminary Results.’, Int J Endocrinol, 2012 408295. PubMed: 22719761
Mendoza-Zubieta, V, et al. (2015), ‘High prevalence of metabolic syndrome in a mestizo group of adult patients with primary hyperparathyroidism (PHPT).’, BMC Endocr Disord, 15 16. PubMed: 25886602
Murray, SE, et al. (2014), ‘Improvement of sleep disturbance and insomnia following parathyroidectomy for primary hyperparathyroidism.’, World J Surg, 38 (3), 542-48. PubMed: 24142330
Ojeda López, R, et al. (2017), ‘Correction of 25-OH-vitamin D deficiency improves control of secondary hyperparathyroidism and reduces the inflammation in stable haemodialysis patients.’, Nefrologia, PubMed: 28673686
Perrier, ND (2005), ‘Asymptomatic hyperparathyroidism: a medical misnomer’, Surgery, 137 (2), 127-31. PubMed: 15674190
Repplinger, D, et al. (2009), ‘Neurocognitive dysfunction: a predictor of parathyroid hyperplasia.’, Surgery, 146 (6), 1138-43. PubMed: 19958941
Suliburk, JW and ND Perrier (2007), ‘Primary hyperparathyroidism.’, Oncologist, 12 (6), 644-53. PubMed: 17602056
Yoo, JY, et al. (2016), ‘Does impotence improve after parathyroidectomy in men with primary hyperparathyroidism’, Surgery, 159 (1), 204-10. PubMed: 26492988