Primary hyperparathyroidism in developing world: a systematic review on the changing clinical profile of the disease.

While the developed world is focusing on laying guidelines for selecting out cases of Asymptomatic primary hyperparathyroidism (PHPT) for surgical intervention and promoting minimal access surgery, the developing world is observing a change in disease spectrum from advanced symptomatic to lesser degree of symptomatic disease and not many with associated Vitamin D deficiency. Few studies from the developing countries of the world have focused on the changing clinical spectrum of PHPT. Objective of this study is to review the changing profile of PHPT in developing world. A systematic literature search was done in December 2017 focussing on publications from the developing world. All studies pertaining to the epidemiology of PHPT published after 1st January 2000 and published in English language were included for analysis. Most of the studies published from developing countries report a predominance of symptomatic disease (79.6% of all included patients) with musculoskeletal disease present in the majority of patients (52.9%). The combined mean serum total calcium (11.9 ± 1.4 mg/dL), serum PTH (668.6 ± 539 pg/mL), serum alkaline phoshpatase (619 ± 826.9 IU/L) and weight of excised parathyroid glands (4.4 ± 3.8 grams) are much higher than those reported from the western studies. Despite this, we found that there is a distinct trend towards a milder form of disease presentation and biochemical profile noticeable in more recent times. Although there is a striking difference in all aspects of PHPT disease epidemiology, clinical presentation and biochemical profile of developing and developed countries, there is a distinct trend towards a milder form of disease presentation and biochemical profile in more recent times.

Primary hyperparathyroidism in developing world: a systematic review on the changing clinical profile of the disease

ABSTRACT While the developed world is focusing on laying guidelines for selecting out cases of Asymptomatic primary hyperparathyroidism (PHPT) for surgical intervention and promoting minimal access surgery, the developing world is observing a change in disease spectrum from advanced symptomatic to lesser degree of symptomatic disease and not many with associated Vitamin D deficiency. Few studies from the developing countries of the world have focused on the changing clinical spectrum of PHPT. Objective of this study is to review the changing profile of PHPT in developing world. A systematic literature search was done in December 2017 focussing on publications from the developing world. All studies pertaining to the epidemiology of PHPT published after 1st January 2000 and published in English language were included for analysis. Most of the studies published from developing countries report a predominance of symptomatic disease (79.6% of all included patients) with musculoskeletal disease present in the majority of patients (52.9%). The combined mean serum total calcium (11.9 ± 1.4 mg/dL), serum PTH (668.6 ± 539 pg/mL), serum alkaline phoshpatase (619 ± 826.9 IU/L) and weight of excised parathyroid glands (4.4 ± 3.8 grams) are much higher than those reported from the western studies. Despite this, we found that there is a distinct trend towards a milder form of disease presentation and biochemical profile noticeable in more recent times. Although there is a striking difference in all aspects of PHPT disease epidemiology, clinical presentation and biochemical profile of developing and developed countries, there is a distinct trend towards a milder form of disease presentation and biochemical profile in more recent times.

Primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT), the most common cause of hypercalcemia, is most often identified in postmenopausal women with hypercalcemia and parathyroid hormone (PTH) levels that are either frankly elevated or inappropriately normal. The clinical presentation of PHPT includes three phenotypes: target organ involvement of the renal and skeletal systems; mild asymptomatic hypercalcemia; and more recently, high PTH levels in the context of persistently normal albumin-corrected and ionized serum calcium values. The factors that determine which of these three clinical presentations is more likely to predominate in a given country include the extent to which biochemical screening is employed, the prevalence of vitamin D deficiency, and whether a medical center or practitioner tends to routinely measure PTH levels in the evaluation of low bone density or frank osteoporosis. When biochemical screening is common, asymptomatic primary hyperparathyroidism is the most likely form of the disease. In countries where vitamin D deficiency is prevalent and biochemical screening is not a feature of the health care system, symptomatic disease with skeletal abnormalities is likely to predominate. Finally, when PTH levels are part of the evaluation for low bone mass, the normocalcemic variant is seen. Guidelines for surgical removal of hyperfunctioning parathyroid tissue apply to all three clinical forms of the disease. If guidelines for surgery are not met, parathyroidectomy can also be an appropriate option if there are no medical contraindications to surgery. In settings where either the serum calcium or bone mineral density is of concern, and surgery is not an option, pharmacological approaches are available and effective. Referencing in this article the most current published articles, we review the different presentations of PHPT, with particular emphasis on recent advances in our understanding of target organ involvement and management.

Comparative characteristics of primary hyperparathyroidism in pediatric and young adult patients.

BACKGROUND: Primary hyperparathyroidism is rare in pediatric patients. Our study aim was to compare primary hyperparathyroidism in pediatric (<19 years) and young adult (19-29 years) patients. METHODS: A prospectively collected database from a single, high-volume institution was queried for all patients age <30 years who had initial parathyroidectomy for primary hyperparathyroidism yielding 126/4,546 (2.7%) primary hyperparathyroidism patients representing 39 pediatric and 87 young adult patients. Presenting symptoms, operative data, and postoperative course were compared for patients age 0-19 years and 20-29 years. RESULTS: Sporadic primary hyperparathyroidism was present in 81.7% and occurred less often in pediatric patients than young adult patients (74.4% vs 86.2%, P = .12). Among patients with hereditary primary hyperparathyroidism, multiple endocrine neoplasia type 1 was the most common type. Multiglandular disease was common in both pediatric (30.7%) and young adult (21.8%) patients. Following parathyroidectomy, 3 (2.3%) patients had permanent hypoparathyroidism and none had permanent recurrent laryngeal nerve paralysis. Biochemical cure at 6 months was equally likely in pediatric and young adult patients (97.1% vs 93.6%, P = .44) with comparable follow-up (78.4 months vs 69.1 months, P = .66) and rates of recurrent disease (5.9% vs 10.3%, P = .46). Recurrence was due to multiple endocrine neoplasia 1-related primary hyperparathyroidism in all cases. CONCLUSION: Although primary hyperparathyroidism is sporadic in most patients <19 years, they are more likely to have multiple endocrine neoplasia type 1-associated primary hyperparathyroidism (23%). Parathyroidectomy for primary hyperparathyroidism can be performed safely in pediatric patients with a high rate of cure. Follow-up for patients with hereditary disease is necessary.

Hypercalciuria May Persist After Successful Parathyroid Surgery and It Is Associated With Parathyroid Hyperplasia.

CONTEXT: Hypercalciuria is frequently found in primary hyperparathyroidism (1HPT) and, although it generally normalizes after successful parathyroidectomy, may persist in some patients. The factors associated with persistent calcium renal leak (cRL) have not been clarified. OBJECTIVE: The purpose of this study was to determine the prevalence of cRL in our 1HPT population and investigate cRL-related factors. DESIGN: This was a retrospective longitudinal study. SETTING: The study was conducted in an outpatient setting. PATIENTS/INTERVENTION: The participants were 95 patients with 1HPT successfully operated on who had a normal estimated glomerular filtration rate. MAIN OUTCOME MEASURES: The biochemical parameters of calcium metabolism and bone mineral density (BMD) measured by dual-X-ray absorptiometry before and 24 months after surgery were assessed. All histological findings were recorded. RESULTS: The prevalence of hypercalciuria before and after surgery was 74% and 32%, respectively. Before, surgery patients with cRL showed lower calcium and higher phosphate levels than those without cRL (10.9 ± 0.6 vs 11.4 ± 0.8 mg/dL [2.7 ± 0.2 vs 2.8 ± 0.2 mmol/L], P = .01 and 2.6 ± 0.5 vs 2.4 ± 0.4 mg/dL [0.84 ± 0.2 vs 0.77 ± 0.1 mmol/L], P = .04, respectively), whereas 24-h calciuria levels and the prevalence of 1HPT complications (osteoporosis, renal stones, and hypertension) were comparable. After surgery, serum calcium, phosphate, and PTH levels were comparable between patients with and without cRL. The prevalence of the histological finding of parathyroid hyperplasia was higher in patients with cRL (50%) than in patients without cRL (22%) (P = .01). The presence of cRL was independently associated with presurgery hypercalciuria (odds ratio, 4.71; 95% confidence interval, 1.18-18.8; P = .03) and parathyroid hyperplasia (odds ratio, 3.52; 95% confidence interval, 1.31-9.43; P = .01). Only patients without cRL had improved BMD at the spine (P = .04), total femur (P = .01), and femoral neck (P = .01). CONCLUSIONS: cRL is present in 30% of patients with 1HPT after successful surgery, and it is associated with parathyroid hyperplasia before surgery and the lack of improvement in BMD after surgery.

High prevalence of metabolic syndrome in a mestizo group of adult patients with primary hyperparathyroidism (PHPT).

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.

Fibromyalgia symptoms and medication requirements respond to parathyroidectomy.

BACKGROUND: Fibromyalgia (FM), an ill-defined symptom complex, is characterized by musculoskeletal pain, headache, depression, fatigue, and cognitive decline, symptoms also seen commonly in primary hyperparathyroidism (PHP). Prevalence of concurrent PHP and FM and response to parathyroidectomy (PTX) of those with both conditions are unknown. METHODS: We reviewed prospective data of 4,000 patients with sporadic PHP who had PTX from 1995 to 2013 examining perioperative symptoms and medication usage for those with diagnosed FM. Cure was defined by normocalcemia at ≥ 6 months. RESULTS: Of 2,184 patients, 80 (4%) had a prior diagnosis of FM. Of evaluable FM patients, 97.3% had definitive cure of PHP. After PTX, 89% had improvement in ≥ 1 symptom attributed to FM, with improved cognition/memory most common (80%). Improvement in ≥ 2, ≥ 3, and ≥ 4 FM symptoms was appreciated by 71%, 43%, and 25%, respectively. Quality of life and wellness improved in >50%. Postoperative use of drugs prescribed for FM often improved or resolved (narcotics, 77%; anti-inflammatories, 74%; "FM-specific medications," 33%; antidepressants, 30%); 21% discontinued all FM medications postoperatively. CONCLUSION: FM is common in patients operated on for sporadic PHP. Of those with both conditions, after PTX 89% appreciate symptom response and 77% and 21% had a decrease in or discontinuation or medications, respectively. Before diagnosing FM, providers should exclude PHP, which is surgically correctable.

Hiperparatiroidismo primario: manejo quirúrgico / Primary hyperparathyroidism: surgical treatment

Background: Primary hyperparathyroidism (HPTP) is the most common cause of hypercalcaemia in the ambulatory setting. This condition affects between 0.1 -2 percent of the population. Surgery is the only curative treatment. Objective: The aim of the study is to present our 10-year surgical experience. Methods: Analytical-descriptive study. We included all patients diagnosed with HPTP treated with surgery in our hospital between June 2003 and June 2013. Results: 173 patients underwent surgery for HPTP. The mean age was 57.5 +/- 13.5 years. Asymptomatic in 98 cases (56.6 percent). Resection the abnormal parathyroid glands was performed in all cases with intraoperative PTH monitoring. In 167 patients (96.5 percent) intraoperative PTH declined ≥ 50 percent. The median follow-up was 61 months (1-117 months). Cure was achieved in 169 patients (97.7 percent). Four cases (2.3 percent) had recurrence. Conclusions: Surgery is effective and safe for the treatment of HPTP. A decline in intraoperative PTH > 50 percent predicts cure in 97.7 percent of cases.

Introducción: El hiperparatiroidismo primario (HPTP), es una entidad frecuente que afecta entre el 0,1 y 2 por ciento de la población. La cirugía es el único tratamiento curativo. Objetivo: Evaluar la eficacia y riesgos del tratamiento quirúrgico del HPTP. Material y Métodos: Estudio analítico-descriptivo. Se incluyó a todos los pacientes con diagnóstico de HPTP referidos para cirugía al Hospital Clínico de la Pontificia Universidad Católica de Chile entre junio de 2003 y junio de 2013. Resultados: 173 pacientes fueron operados en nuestra institución por HPTP. El promedio de edad de los pacientes fue de 57,5 +/- 13,5 años. La forma de presentación fue asintomática en 98 casos (56,6 por ciento) y sintomática en 75 casos (43,4 por ciento). Todos los pacientes fueron tratados con resección de la o las glándulas hiperfuncionantes con medición de PTH intraoperatoria. En 167 pacientes (96,5 por ciento) se logró caída de PTH intraoperatoria > 50 por ciento. Catorce pacientes (8,1 por ciento) presentaron complicaciones post operatorias. La mediana de hospitalización fue de 2 días (1 a 23 días). La mediana de seguimiento fue de 61 meses (6 a 117 meses). Se logró curación en 169 pacientes (97,7 por ciento). Cuatro casos (2,3 por ciento) presentaron recidiva. Conclusiones: La cirugía es eficaz y segura para el tratamiento del hiperparatiroidismo primario. Una caída de PTH intraoperatoria > 50 por ciento del valor basal predice curación en 97,7 por ciento de los casos.

Frequency of various types of neoplasia in a group of acromegalic patients.

OBJECTIVE: To determine the frequency of colon cancer, primary hyperparathyroidism, thyroid tumor, and skin cancer in all acromegalic patients in follow-up at the Clinics Hospital - Botucatu Medical School, from 2005 to 2011. SUBJECTS AND METHODS: These patients were evaluated retrospectively for colon cancer, primary hyperparathyroidism, dermatological, and thyroid tumors. RESULTS: Of 29 patients included at the beginning of the study, two were excluded. Among 19 patients submitted to colonoscopy, one presented colon adenocarcinoma (5%). Thyroid nodules were present in 63% of patients, and papilliferous carcinoma was confirmed in two patients (7,7%). Four patients were confirmed as having primary hyperparathyroidism (15%). The most common dermatologic lesions were thickened skin (100%), acrochordons (64%), epidermal cysts (50%), and pseudo-acanthosis nigricans (50%). Only one patient presented basal cell carcinoma. CONCLUSION: Although a small number of acromegalic patients was studied, our findings confirm the high frequency of thyroid neoplasias and primary hyperparathyroidism in this group of patients.

Frequency of various types of neoplasia in a group of acromegalic patients / Frequência de neoplasia de diversos tipos em um grupo de pacientes acromegálicos

OBJECTIVE: To determine the frequency of colon cancer, primary hyperparathyroidism, thyroid tumor, and skin cancer in all acromegalic patients in follow-up at the Clinics Hospital - Botucatu Medical School, from 2005 to 2011. SUBJECTS AND METHODS: These patients were evaluated retrospectively for colon cancer, primary hyperparathyroidism, dermatological, and thyroid tumors. RESULTS: Of 29 patients included at the beginning of the study, two were excluded. Among 19 patients submitted to colonoscopy, one presented colon adenocarcinoma (5%). Thyroid nodules were present in 63% of patients, and papilliferous carcinoma was confirmed in two patients (7,7%). Four patients were confirmed as having primary hyperparathyroidism (15%). The most common dermatologic lesions were thickened skin (100%), acrochordons (64%), epidermal cysts (50%), and pseudo-acanthosis nigricans (50%). Only one patient presented basal cell carcinoma. CONCLUSION: Although a small number of acromegalic patients was studied, our findings confirm the high frequency of thyroid neoplasias and primary hyperparathyroidism in this group of patients.

OBJETIVO: Determinar a frequência de câncer de cólon, hiperparatireoidismo primário, tumores de tireoide e pele em todos os acromegálicos em seguimento no Hospital de Clínicas da Faculdade de Medicina de Botucatu de 2005 a 2011. SUJEITOS E MÉTODOS: Esses pacientes foram avaliados retrospectivamente quanto a presença de câncer de cólon, hiperparatiroidismo primário, tumores da tiroide e pele. RESULTADOS: Dos 29 pacientes incluídos no início do estudo, dois foram excluídos. Dentre os 19 pacientes submetidos à colonoscopia, um apresentou adenocarcinoma de cólon (5%). Nódulos de tireoide estiveram presentes em 65% dos pacientes e carcinoma papilífero, em dois deles (7,7%). Quatro pacientes apresentaram hiperparatireoidismo primário (15%). A maioria das lesões de pele foram: espessamento (100%), acrochordons (64%), cistos epidérmicos (50%), pseudoacantose nigricans (50%) e apenas um paciente apresentou carcinoma basocelular. CONCLUSÃO: O tamanho da amostra é pequeno, mas nossos achados confirmam a alta frequência da neoplasia da tireoide e hiperparatireroidismo neste grupo de pacientes.

Normocalcemic primary hyperparathyroidism in clinical practice: an indolent condition or a silent threat?

OBJECTIVE: To describe the characteristics of normocalcemic primary hyperparathyroidism (NPHPT) in patients seen for osteoporosis evaluation. PATIENTS AND METHODS: We examined the records of 156 women who came to the hospital to be screened for osteoporosis. Measurements of total calcium, PTH, 25-hydroxy vitamin D, and ß-C-telopeptide were recorded. Bone mineral density and T-scores were evaluated by densitometry of the lumbar spine, femoral neck and distal one-third of the radius. The latter was only measured in patients with primary hyperparathyroidism. Nephrolithiasis and bone fractures were documented by a review of the medical records. RESULTS: We identified 14 patients with NPHPT, accounting for 8.9% of the population studied. In the medical records, the occurrence of kidney stones was reported in 28.6% of the patients with NPHPT, in contrast with only 0.7% of the noncarriers. Regarding the presence of general fractures, 21.4% of the patients with NPHPT were affected versus 16.2% of noncarriers. CONCLUSION: Data from our study suggest that NPHPT has a diverse phenotypic presentation, implying that this may not be an "indolent" disease.

Normocalcemic primary hyperparathyroidism in clinical practice: an indolent condition or a silent threat? / Hiperparatireoidismo primário normocalcêmico na prática clínica: condição indolente ou ameaça silenciosa?

OBJECTIVE: To describe the characteristics of normocalcemic primary hyperparathyroidism (NPHPT) in patients seen for osteoporosis evaluation. PATIENTS AND METHODS: We examined the records of 156 women who came to the hospital to be screened for osteoporosis. Measurements of total calcium, PTH, 25-hydroxy vitamin D, and β-C-telopeptide were recorded. Bone mineral density and T-scores were evaluated by densitometry of the lumbar spine, femoral neck and distal one-third of the radius. The latter was only measured in patients with primary hyperparathyroidism. Nephrolithiasis and bone fractures were documented by a review of the medical records. RESULTS: We identified 14 patients with NPHPT, accounting for 8.9 percent of the population studied. In the medical records, the occurrence of kidney stones was reported in 28.6 percent of the patients with NPHPT, in contrast with only 0.7 percent of the noncarriers. Regarding the presence of general fractures, 21.4 percent of the patients with NPHPT were affected versus 16.2 percent of noncarriers. CONCLUSION: Data from our study suggest that NPHPT has a diverse phenotypic presentation, implying that this may not be an "indolent" disease.

OBJETIVO: Avaliar as características do hiperparatireoidismo primário normocalcêmico (HPTPN) em pacientes atendidos para avaliação de osteoporose. PACIENTES E MÉTODOS: Foi realizada análise de um banco de dados de 156 mulheres que procuraram atendimento para avaliação de osteoporose. Todas apresentavam dosagem de cálcio sérico, PTH, 25-hidroxi-vitamina D e C-telopeptídeo. A densidade mineral óssea e escore-T foram avaliados por meio de densitometria óssea de coluna lombar, colo do fêmur e rádio distal, este último apenas em pacientes com hiperparatireoidismo renal primário. Nefrolitíase e fraturas ósseas foram documentadas pela revisão dos prontuários. RESULTADOS: Foram identificadas 14 pacientes com HPTPN, correspondendo a 8,9 por cento da população estudada. Nos registros médicos, o relato da existência de litíase renal ocorreu em 28,6 por cento dos portadores de HPTN em contraste com apenas 0,7 por cento nas mulheres não portadoras, com um p < 0,001. CONCLUSÃO: Os dados do estudo sugerem que HPTPN tem uma apresentação fenotípica variada, podendo não ser uma patologia "indolente".

Long-term effects of parathyroidectomy on hypertension prevalence and circadian blood pressure profile in primary hyperparathyroidism.

Our aims were to evaluate the prevalence and outcome of hypertension in patients with primary hyperparathyroidism (PHPT), previously and after follow-up of parathyroidectomy. A group of 46 consecutive patients with sporadic PHPT due to adenoma undergoing surgery were followed an average of 3.5 years (range 36 to 53 months). In 16 nonselected, consecutive parathyroidectomized patients, with normalized biochemical measurements, circadian rhythm of blood pressure was evaluated with ambulatory blood pressure monitoring (ABPM). Prevalence of hypertension in PHPT was 54.35%, and there was no significant association of PTH, total and ionic calcium levels with SBP and DBP. During follow-up, none of the patients with presurgical hypertension became normotensive and five of the normotensive patients developed clinical hypertension. In ABPM, 6/11 hypertensive and 3/5 normotensive subjects showed nondipper behavior. Serum total calcium was significantly related to night-time systolic blood pressure (SBP) (r = 0.620, P < 0.02), and night-time diastolic blood pressure (DBP) (r = 0.758, P < 0.002). In dippers, creatinine clearance was significantly higher (91.3 +/- 18.5 vs. 64.3 +/- 11.5 ml/min, P < 0.01), while serum total calcium was lower (2.42 +/- 0.13 vs. 2.23 +/- 0.17 mmol/L, P < 0.04) than in nondippers. In conclusion, our results suggest that parathyroidectomy has little effect on hypertension prevalence. Renal impairment, a condition that did not improve after parathyroidectomy, may be a causal factor of hypertension in PHPT. Also, the high prevalence of nondipper behavior in hypertensive and normotensive subjects after parathyroidectomy, suggests that target organ risk persists. We hypothesized that slight elevations of serum total calcium even in the normal range could be involved in the alteration of the circadian rhythm of blood pressure.