|Year : 2018 | Volume
| Issue : 1 | Page : 22-25
Modes of presentation of primary hyperparathyroidism in Al Hawari General Hospital, Benghazi-Libya
Muftah S Elsaeiti1, Fadia S Akhreim2, Khaled D Alsaeiti3
1 Department of Endocrine and Internal Medicine, Faculty of Medicine, Benghazi, Libya
2 Faculty of Medicine, Benghazi University, Benghazi, Libya
3 Department of Medicine, Jamhoryia Hospital, Benghazi, Libya
|Date of Web Publication||27-Mar-2018|
Dr. Khaled D Alsaeiti
Faculty of Medicine, Benghazi University, Benghazi
Source of Support: None, Conflict of Interest: None
Background: Primary hyperparathyroidism (PHPT) is an endocrine disorder with variable clinical expression, frequently presenting as asymptomatic hypercalcemia in western countries but still predominantly as symptomatic disease in developing countries. The objective of this retrospective study was to describe the modes of presentation of this disease in Benghazi. Patients and Methods: Records of nineteen patients diagnosed with PHPT at metabolic bone disease clinic of Al Hawari general hospital, Benghazi, Libya, during 2005–2012 were reviewed. Results: Mean age at diagnosis was 41.7 ± 11.5 (range 20–70 years). There were 17 females and 2 males with a ratio of 8.5:1. Eighteen patients (94.7%) were symptomatic. Skeletal manifestations were the major mode of presentation in seventeen patients (89.4%) followed by renal stone in one patient (5.3%). All symptomatic patients had a single adenoma, nine of them (47.4%) had right inferior adenomas, and nine had left inferior ones (47.7%), and no adenoma can be detected in asymptomatic patient (5.3%). More than half of the patients had normal serum calcium levels (52.6%) at the time of diagnosis and (47.3%) had persistent hypercalcemia with a mean serum calcium level (10.7 ± 1.02 mg/dL), all patients had high serum intact parathyroid hormone with a mean value of (696.3 ± 379.5 pg/mL), and high serum alkaline phosphatase with a mean level of (901.9 ± 520.8U/L) except one patient who had low level of 20U/L. Vitamin D was measured only in six patients, five of them were a deficit, and one asymptomatic patient had normal level. All our patient's parathyroid adenomas were localized by Ultrasound. Seventeen patients had successful surgery, one patient had a recurrence, and one asymptomatic patient was managed medically according to the Third International Workshop guidelines. Conclusions: PHPT in Libya continues to be a severe, symptomatic disorder with skeletal, and renal manifestations at a much younger age.
Keywords: Hypercalcemia, parathyroid adenoma, primary hyperparathyroidism
|How to cite this article:|
Elsaeiti MS, Akhreim FS, Alsaeiti KD. Modes of presentation of primary hyperparathyroidism in Al Hawari General Hospital, Benghazi-Libya. Libyan J Med Sci 2018;2:22-5
|How to cite this URL:|
Elsaeiti MS, Akhreim FS, Alsaeiti KD. Modes of presentation of primary hyperparathyroidism in Al Hawari General Hospital, Benghazi-Libya. Libyan J Med Sci [serial online] 2018 [cited 2018 May 23];2:22-5. Available from: http://www.ljmsonline.com/text.asp?2018/2/1/22/228677
| Introduction|| |
Primary hyperparathyroidism (pHPT) is a common disorder that arises from autonomous overproduction of parathyroid hormone (PTH) by abnormal parathyroid glands. The disease is characterized by the persistent elevation of total serum calcium levels with corresponding elevated or inappropriately normal (i.e., nonsuppressed) PTH levels. The diagnosis of is biochemical. The clinical presentation is heterogeneous, and the associated symptoms overlap with those of aging and disease. Patients with symptomatic pHPT have overt signs and symptoms; however, the definition of symptomatic disease is still evolving. Patients with asymptomatic pHPT have no disease-specific symptoms.
PHPT is the most common cause of hypercalcemia in an outpatient. It is the third most common endocrinopathy , seen today after diabetes mellitus and thyroid disease.
The various case studies worldwide show an annual incidence of 20 cases per 100,000 people with an estimated prevalence in the general population of 0.5% to 1% increasing with age over 2% in both sexes., It occurs 2–3 times more frequently in women than in men and has a higher prevalence in postmenopausal women.
There are geographical differences in age distribution, in western countries, PHPT mainly affects middle-aged patients with peak incidence in the sixth to seventh decades of life, but in developing countries, it is more common in younger age groups.
Mortality and morbidity were increased for patients with mild untreated PHPT, which is similar to more severe PHPT.
The main cause is represented by a solitary parathyroid adenoma (80%–85% of cases), the remaining 15%–20% of cases are represented by conditions of diffuse glandular hyperplasia and multiple adenomas. A small percentage of patients presents with typical familial forms of multiple endocrine neoplasia (MEN 1 and MEN 2A) syndromes.
The current study aims to describe the modes of clinical presentation of PHPT among Libyan patients seen at metabolic bone disease clinics in Benghazi.
| Patients and Methods|| |
Case series study in which the records of all diagnosed PHPT cases from January 2005 to December 2012 based on biochemical results were retrieved from the patient's files at metabolic bone disease clinic of Al Hawari General hospital, Benghazi-Libya, in which nineteen patients (17 females and 2 males) were diagnosed with PHPT. For each patient, the following data was obtained: age, gender, clinical presentation (skeletal, renal, and others), laboratory data included serum calcium (normal range 8.6–10.2 mg/dl) by Enzymatic Chlorometric (Cobas C311, Switzerland), serum intact parathyroid hormone (iPTH) (normal range 15–65 pg/ml) by Immunoassay (Cobas 6000, Germany), and serum alkaline phosphatase (normal range 40–129 U/L) by Enzymatic Chlorometric (Cobas C311, Switzerland), and Vitamin D (25-OHD3) was measured in six patients, normal range (21–29 ng/ml) by Immunoassay (Cobas 6000, Germany). Radiological localization methods were performed and the site of adenoma was noted. Other radiological findings as bone fracture and renal stones were also noted. Data about management, operative findings (either single, multiple, or ectopic adenoma) was also collected.
Statistical Package for Social Sciences (SPSS) software (version 17, IBM, Armonk, NY, United States of America). Frequency tables were analyzed using the Chi-square test and P values being used to assess the significance of the correlation between the categorical variable. In all tests, the values P < 0.05 were regarded statistically significant.
| Results|| |
An overwhelming majority (17/19; 89.5%) of the patients were females giving a male:female ratio of 1:8.5. The mean age of patients was 41.7 ± 11.5 with a range of 30–50 years and peak incidence was in the third to fifth decades of life. The mean duration of symptoms before diagnosis was (2–10) years.
The vast majority of patients (18/19, 94.7%) were symptomatic skeletal manifestations (proximal muscle weakness, bone pain, bone cyst, and bone fracture) were the most common presentation, seen in 17 (89.4%) patients (P< 0.05), two of them were bedbound for 8 and 10 years, respectively, and were diagnosed as osteomalacia at first. Renal manifestations were the least frequent complaint, only one patient (5.3%). None of the patients presented with gastrointestinal disturbances such as constipation, nausea or vomiting, and there were no documented cases of neuropsychiatric manifestations.
All the patient's adenoma was localized by neck ultrasound. Single adenoma was involved in 18 cases (94.7%), and one asymptomatic case had no adenoma. Among these 18 cases, 9 (47.7%) were right inferior in location, while 9 (47.4%) were left inferior.
Nine patients (47.7%) had persistent hypercalcemia, 10 patients (52.6%) had normal serum calcium at time of diagnosis. Mean serum calcium level was (10.7 ± 1.02 mg/dl). All patients had high iPTH with mean values of (696.3 ± 379.5 pg/mL). The serum total ALP was elevated (>140 IU/L) in (94.7%) of patients. The mean serum ALP was (901.9 ± 520.8 U/L). Vitamin D (25-OHD3) was measured in six patients and five of them were deficient [Table 1].
|Table 1: Age and gender distribution of clinical characteristics of primary hyperparathyroidism patients|
Click here to view
Most of the patients displayed radiographic changes suggestive of hyperparathyroid bone disease. DXA scan was not available in all patients, it was reported only in five patients, four of them had Osteopenia while the other was asymptomatic with normal DXA scanning. Pathologic fractures were evident in eight patients. Common sites of fractures were pelvic and long bones. Renal disease was present in one patient (5.3%). The pattern of kidney involvement was nephrolithiasis.
Eighteen of patients managed surgically by traditional 4-gland neck exploration with the identification of a single adenoma and its removal with histopathological confirmation. Successful parathyroidectomy led to cure in 17 patients, and failed in one case, in which ectopic adenoma was suspected. Postoperative hungry bone syndrome (HBS) was observed in six patients. One asymptomatic patient was managed medically according to the Third International Workshop guidelines for the management of asymptomatic PHPT.
There was one patient died during the study because of stone-induced acute renal failure.
| Discussion|| |
We point that only nineteen patients were diagnosed between 2005 and 2012 at a reference public service. We believe that this low figure could be related to a delayed pHPT diagnosis and to a delayed pHPT diagnosis and to a still low recognition of the disease.
As shown in the current study, female patients had higher rates of pHPT as compared to males (89.5% and 10.5%, respectively), and the mean age of patients was 41.7 ± 11.5 years, with a peak incidence in the third to fifth decades, which is two decades earlier than that in developed countries. This is in alignment with previous reports from other developing countries where the mean age reported was <50.,,, The story is completely different in developed countries, in which hyperparathyroidism mainly affects middle-aged patients with a peak incidence in the sixth to seventh decades of life and a female to male ratio of 2–3:1.,,,
One of the most important findings of the current study is that eighteen patients (94.7%) were symptomatic, seventeen of them (89.4%) came with musculoskeletal manifestations, and one (5.3%) with renal symptoms. This finding also comparable with observations in most developing countries. In Brazil, similar observation has been previously reported by Oliveria et al. who found that 66% of patients were symptomatic. Furthermore, similar observations have been reported in other developing countries, such as Saudi Arabia and Iran., It is not clear why our patients present at a younger age, and why they are symptomatic, some researchers explained the high percentage of bone involvement with florid presentation in developing countries by common coexistence of Vitamin D deficiency, prolonged PHPT, and low calcium intake. Low serum Vitamin D levels in patients with PHPT were associated with worsening laboratory, densitometric, and histomorphometric indices of bone involvement and a high risk of fractures. Likewise, results of many studies have shown that coexisting Vitamin D deficiency might result in advanced osteitis fibrosa cystica.
Renal disease is considerably less frequent in our patients which is consistent with studies from other developing countries.,
In western countries, nephrolithiasis is still its most common complication, but kidney stones (KS) are less prevalent than they used to be. However, very few studies have focused on the frequency of KS through imaging technology in asymptomatic subjects. Retrospective data give a prevalence range of KS between 7 and 11% when abdominal ultrasound is utilized. By spiral computed tomography, Starup-Linde et al. reported the prevalence of 15.2% and 10.1% for nephrolithiasis and nephrocalcinosis, respectively. The low frequency of renal involvement in patients from developing countries could be attributed to the absence of significant hypercalciuria, due to a low mean serum calcium levels, most probably resulting from low dietary calcium consumption and/or Vitamin D deficiency; supporting this is the high prevalence of normocalcemic PHPT in many studies from developing countries where its prevalence has been reported from range between 3% and 50%.
Surprisingly, in our study, there were 10 (52.6%) of nineteen patients had serum calcium level within the normal range at the time of diagnosis, and only nine patients (47.4%) had persistent hypercalcemia, with a mean serum calcium level (10.7 ± 1.02). this is may be explained in part by coexistence of Vitamin D deficiency or by high prevalence of normocalcemic PHPT in our country, further studies are needed with measurement of serum Vitamin D and replacement if it is deficit to know the cause of normal serum calcium in our patients. It has been reported that patients may present with serum calcium levels within normal ranges but normocalcemic hyperparathyroidism in individuals with one and/or kidney involvement is a rare finding in the west, in contrast to the prevalence of normocalcemic hyperparathyroidism, reported to range from 3% to 50% in developing countries.
All our patients had single parathyroid adenoma which was localized by neck ultrasound. One asymptomatic patient had normal neck USS, and among 18 cases, nine patients had right inferior adenomas, and nine patients had left inferior parathyroid adenomas. There is only one study evaluated the location of the parathyroid adenoma by Marzouki et al. in Monereal between 2001 and 2010. In this study, there were 121 patients with confirmed adenomas, 50 of them had left inferior parathyroid adenomas, and 40 patients had right inferior adenomas. This information may provide parathyroid surgeon with a starting point when imaging fails to localize the site of the adenoma, which allows for the possibility of minimally invasive surgery, especially if used in conjunction with intraoperative parathyroid hormone.
In our study, Vitamin D measurement was not possible to all cases. It was measured only in six patients, five of them were deficient, and one was normal. Unfortunately, we could not give full information about Vitamin D status in our patients.
Six out of eighteen operated cases developed HBS postoperatively. Witteveen et al. conducted a systemic review of literatures reporting a “hungry bone syndrome” post parathyroidectomy for PHPT, they found that the syndrome is reported in 25%–90% of patients with radiological evidence of hyperparathyroid bone disease versus only 0%–6% of patients without skeletal involvement.
There was one female died during the study after successful parathyroidectomy, because of stone-induced acute renal failure. Mortality may still remain increased after PTX in overt PHPT, albeit that risk gradually begins to improve approximately 5 years after surgery. for patients undergoing PTX with mild PHPT, improvements in BMD and dyslipidemia, but not mortality, have been demonstrated.
| Conclusions|| |
Within the limits of this retrospective study, we found that PHPT is a severe, symptomatic disease with serious complications among Libyans. The advanced skeletal disease is the most common pattern of presentation at a young age. Furthermore, Vitamin D deficiency may be an unrecognized public health problem among Libyan population. There is a compelling need to take public health measures to improve Vitamin D status in this part of Libya.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Wilhelm SM, Wang TS, Ruan DT, Lee JA, Asa SL, Duh QY, et al.
The American Association of Endocrine Surgeons guidelines for definitive management of primary hyperparathyroidism. JAMA Surg 2016;151:959-68.
Pallan S, Khan A. Primary hyperparathyroidism: Update on presentation, diagnosis, and management in primary care. Can Fam Physician 2011;57:184-9.
Fraser WD. Hyperparathyroidism. Lancet 2009;374:145-58.
Pyram R, Mahajan G, Gliwa A. Primary hyperparathyroidism: Skeletal and non-skeletal effects, diagnosis and management. Maturitas 2011;70:246-55.
Clarke BL. Epidemiology of primary hyperparathyroidism. J Clin Densitom 2013;16:8-13.
Minisola S. Primary hyperparathyroidism is one of the three most frequent endocrine disorders, typically diagnosed in the years following menopause and with advancing age. J Endocrinol Invest 2012;35:1.
Percivale A, Gnerre P, Damonte G, Buscaglia S, Monachesi M, Parodi L, et al
. Primary hyperparathyroidism: Epidemiology, clinical features, diagnostic tools and current management. Ital J Med 2015;9:330-45.
Richert L, Trombetti A, Herrmann FR, Triponez F, Meier C, Robert JH, et al.
Age and gender distribution of primary hyperparathyroidism and incidence of surgical treatment in a European country with a particularly high life expectancy. Swiss Med Wkly 2009;139:400-4.
Yu N, Donnan PT, Flynn RW, Murphy MJ, Smith D, Rudman A, et al.
Increased mortality and morbidity in mild primary hyperparathyroid patients. The Parathyroid Epidemiology and Audit Research Study (PEARS). Clin Endocrinol (Oxf) 2010;73:30-4.
Stuart HC, Harvey A, Pasieka JL. Normocalcemic hyperparathyroidism: Preoperatively a disease, postoperatively cured? Am J Surg 2014;207:673-80.
Elsaeiti M, Abuzaloot T. “Late presentation of primary hyperparathyroidism. In Eighth Libyan Diabetes and Endocrinology Conference; Benghazi, Libya 2010. Salhin A, Eltabal S, Habeb A, Beshyah S, (eds). Ibnosina Journal of Medicine and Biomedical Sciences 2010;212-36.
Malabu UH, Founda MA. Primary hyperparathyroidism in saudi arabia: A review of 46 cases. Med J Malaysia 2007;62:394-7.
Atefi S. Primary hyperparathyroidism in Shiraz. Iran J Endocrinol Metab 2001;3:277-80.
Bahrami A. Primary hyperparathyroidism in Iran: A review. Int J Endocrinol Metab 2008;1:50-7.
Khan A, Bilezikian J. Primary hyperparathyroidism: Pathophysiology and impact on bone. CMAJ 2000;163:184-7.
Oliveira UE, Ohe MN, Santos RO, Cervantes O, Abrahão M, Lazaretti-Castro M, et al.
Analysis of the diagnostic presentation profile, parathyroidectomy indication and bone mineral density follow-up of Brazilian patients with primary hyperparathyroidism. Braz J Med Biol Res 2007;40:519-26.
Mishra SK, Agarwal G, Kar DK, Gupta SK, Mithal A, Rastad J, et al.
Unique clinical characteristics of primary hyperparathyroidism in India. Br J Surg 2001;88:708-14.
Rao DS, Agarwal G, Talpos GB, Phillips ER, Bandeira F, Mishra SK, et al.
Role of vitamin D and calcium nutrition in disease expression and parathyroid tumor growth in primary hyperparathyroidism: A global perspective. J Bone Miner Res 2002;17 Suppl 2:N75-80.
Tordjman KM, Yaron M, Izkhakov E, Osher E, Shenkerman G, Marcus-Perlman Y, et al.
Cardiovascular risk factors and arterial rigidity are similar in asymptomatic normocalcemic and hypercalcemic primary hyperparathyroidism. Eur J Endocrinol 2010;162:925-33.
Fouda MA. Primary hyperparathyroidism: King Khalid University Hospital experience. Ann Saudi Med 1999;19:110-5.
Silverberg SJ, Clarke BL, Peacock M, Bandeira F, Boutroy S, Cusano NE, et al.
Current issues in the presentation of asymptomatic primary hyperparathyroidism: Proceedings of the Fourth International Workshop. J Clin Endocrinol Metab 2014;99:3580-94.
Starup-Linde J, Waldhauer E, Rolighed L, Mosekilde L, Vestergaard P. Renal stones and calcifications in patients with primary hyperparathyroidism: Associations with biochemical variables. Eur J Endocrinol 2012;166:1093-100.
Paruk IM, Esterhuizen TM, Maharaj S, Pirie FJ, Motala AA. Characteristics, management and outcome of primary hyperparathyroidism in South Africa: A single-centre experience. Postgrad Med J 2013;89:626-31.
Jervis L, James M, Howe W, Richards S. Osteolytic lesions: Osteitis fibrosa cystica in the setting of severe primary hyperparathyroidism. BMJ Case Rep 2017;2017:pii: bcr-2017-220603.
Marzouki HZ, Chavannes M, Tamilia M, Hier MP, Black MJ, Levental M, et al.
Location of parathyroid adenomas: 7-year experience. J Otolaryngol Head Neck Surg 2010;39:551-4.
Witteveen JE, van Thiel S, Romijn JA, Hamdy NA. Hungry bone syndrome: Still a challenge in the post-operative management of primary hyperparathyroidism: A systematic review of the literature. Eur J Endocrinol 2013;168:R45-53.
Marcocci C, Brandi ML, Scillitani A, Corbetta S, Faggiano A, Gianotti L, et al
. Italian Society of Endocrinology Consensus Statement: Definition, evaluation and management of patients with mild primary hyperparathyroidism. Journal of endocrinological investigation 2015;38:577-93.
Iakushko O. The modern concept of morphological and functional features of the endocrine glands. World Med Biol J 2016;4:153-9.