Medullary sponge kidney and hyperparathyroidism

Medullary sponge kidney (MSK), parathyroid adenoma, renal cell carcinoma, and renal-leak hypercalciuria coincided in 1 female patient. Renal-leak hypercalciuria was not corrected by removal of a parathyroid adenoma. Since the patient had renal tubular acidosis (RTA), alkali treatment was conducted and resulted in the correction of hypercalciuria. Renal cell carcinoma eventually developed and MSK was confirmed histologically. This case suggests that MSK and primary hyperparathyroidism occurred independently.     

Die parathyreotoxische Krise – ein chirurgischer Notfall

INTRODUCTION: The extremely rare but life-threatening hypercalcemic crisis is caused by an exacerbation of a chronic hyperparathyroidism. The etiologic reasons for this exacerbation are conditions which increase the serum calcium level in addition to the hyperparathyroidism with a complete breakdown of the calcium homeostasis, e. g. malignant tumors, primary and tertiary hyperparathyroidism, vitamin D poisoning or overdoses of calcium, vitamin D and calcium-containing ionizer in patients with renal insufficiency. METHODS: We present the clinical course of five patients with an acute hypercalcemic crisis and discuss the diagnostic procedure and the principles of surgical treatment with regard to the current literature. RESULTS: A hypercalcemic crisis develops if the total serum calcium concentration is over 4 mmol/l and parathormone over 90 pmol/l. The resulting syndrome is manifested by nausea and vomiting, polyuria and consecutive dehydration and hypotonia culminating in lethargy, hallucinations and coma. Hypercalcemia is the single most important diagnostic finding. CONCLUSION: The emergency therapy predominantly consists on the one hand in rehydration and parallel stimulation of diuresis. Urgent surgery is required if conservative therapy is not successful.     

Protein turnover in skeletal muscle tissue from patients with hyperparathyroidism and the effect of calcium in vitro

Protein synthesis and degradation rates in muscle tissue from hypercalcemic and normocalcemic patients were compared. Both protein synthesis and degradation rates were similar in muscle tissue from patients with hyperparathyroidism and age-matched, normocalcemic patients. When Ca++ concentration in the incubation medium was increased, protein breakdown was stimulated in muscle tissue from normocalcemic and hypercalcemic patients, while protein synthesis was increased only in muscle tissue from hypercalcemic patients. The results indicate that protein turnover in muscle tissue is not affected by varying serum calcium levels, but can be regulated by increased Ca++ concentration in vitro.     

Initial failure of surgical exploration in patients with primary hyperparathyroidism

To determine the causes of failures of cervical exploration for primary hyperparathyroidism, we reviewed 892 patients operated on by one surgeon from 1953 to 1990. Twenty-seven patients (3%) remained hypercalcemic or developed hypercalcemia within 6 months of surgery. Of these, five patients had one adenoma removed initially; at reoperation, three patients had a second adenoma that was successfully removed, whereas the other two patients had hyperplasia and required subtotal parathyroidectomies. No enlarged parathyroid glands were identified in 22 patients. Eventually, six patients became normocalcemic spontaneously, seven patients underwent re-exploration with a successful outcome in all but one case, two patients had ectopic hyperparathyroidism associated with carcinoma elsewhere, and seven patients refused reoperation and remain hypercalcemic. The failure rate of surgical exploration for primary hyperparathyroidism can be reduced by systematically exploring all four parathyroid glands. All abnormal parathyroids should be removed with histologic verification. When no abnormal glands are found, localization studies should be performed before re-exploration.     

Hyperparathyroidism in Patients With X-Linked Hypophosphatemia

X-linked hypophosphatemia (XLH) is characterized by increased activity of circulating FGF23 resulting in renal phosphate wasting and abnormal bone mineralization. Hyperparathyroidism may develop in XLH patients; however, its prevalence, pathogenesis, and clinical presentation are not documented. This observational study (CNIL 171036 v 0) recruited XLH adult patients in a single tertiary referral center. Each patient was explored in standardized conditions and compared with two healthy volunteers, matched for sex, age, and 25-OH vitamin D concentrations. The primary endpoint was the proportion of patients with hyperparathyroidism. The secondary endpoints were the factors influencing serum parathyroid hormone (PTH) concentrations and the prevalence of hypercalcemic hyperparathyroidism. Sixty-eight patients (51 women, 17 men) were enrolled and matched with 136 healthy volunteers. Patients had higher PTH concentrations compared with healthy controls (53.5 ng/L, interquartile range [IQR] 36.7–72.7 versus 36.0 ng/L, IQR 27.7–44.0, p < .0001). Hyperparathyroidism was observed in 17 patients of 68 (25%). In patients, a positive relationship between PTH and calcium concentrations and a negative relationship between PTH and phosphate concentrations were observed. Seven (10%) patients (3 premenopausal women, 1 postmenopausal woman, and 3 men) were diagnosed with hypercalcemic hyperparathyroidism. All underwent parathyroid surgery, with consecutive normalization of calcium and PTH concentrations. Hyperparathyroidism is a frequent complication in XLH adult patients. Disruption of the physiological regulation of PTH secretion contributes to parathyroid disease. Early-onset hypercalcemic hyperparathyroidism can be effectively and safely cured by surgical resection. © 2020 American Society for Bone and Mineral Research.     

Hypercalcemic crisis due to unsuspected parathyroid adenoma in a patient with advanced breast carcinoma

Primary hyperparathyroidism was found to be responsible for hypercalcemic crisis in a 73-year-old woman who had undergone mastectomy for advanced breast carcinoma. Medical management followed by removal of a large parathyroid adenoma resulted in gradual recovery and normocalcemia documented over a period of 2 years.     

Outcome after Surgery for Primary Hyperparathyroidism: Ten-year Prospective Follow-up Study

Clinical outcome after surgery for primary hyperparathyroidism was evaluated in a prospective long-term, follow-up study. From August 1, 1987 to August 31, 1998 a total of 360 patients were prospectively investigated and included in a follow-up study. All patients underwent follow-up examinations at regular surveillance intervals. The postoperative course is known for 94.5% of all patients. Follow-up was 1 month to 10 years (median 24 months; mean 34.5 ± 29.8 months). Asymptomatic primary hyperparathyroidism was rare (6%), and its true frequency could be confirmed only postoperatively because some of the patients were unaware of mild symptoms of hypercalcemic syndrome prior to surgery. Surgical cure was obtained in 97.7% of patients after initial cervical exploration; and successful parathyroidectomy provided long-term relief of symptoms. Within 2 years postoperatively, 84% of the patients recovered fully from hypercalcemic syndrome; in 58% of these patients recovery occurred within the first month after surgery. Skeletal symptoms persisted in 24% of patients 2 years postoperatively. To date no patient has developed recurrence of primary hyperparathyroidism. During follow-up in our study population mortality was significantly higher than the expected mortality risk for the German population as a whole (p= 0.00024). The present prospective follow-up study yielded conclusive outcome research data after operative therapy for primary hyperparathyroidism. The high cure rate and low morbidity, as well as the increased mortality, in our study population during follow-up after successful operative therapy for the disease emphasize the importance of early diagnosis and early surgical treatment for primary hyperparathyroidism, even in the absence of manifest symptoms.     

Severe hypercalcemia due to acute primary hyperparathyroidism: role if parathyroidectomy

Grave hypercalcemia may complicate primary hyperparathyroidism. This clinical condition is potentially life-threatening, if it is untreated. The emergency therapy consist in rehydratation, stimulation of diuresis and somministration of biphosphonates. A urgent surgery is required if conservative therapy is not successful. The Authors herein present a consecutive series of 6 cases with acute hypercalcemic crisis due primary hyperparathyroidism, successful treated with urgent parathyroidectomy after conservative treatment.     

Surgical findings and results of subtotal and total parathyroidectomy in hypercalcemic patients with uremic hyperparathyroidism

Surgical and histopathologic findings and results of subtotal resection and total parathyroidectomy with autotransplantation were evaluated in 82 hypercalcemic patients with uremic hyperparathyroidism. The mean preoperative serum calcium concentration was 2.89 mM, and the highest values were associated with more rapidly progressing hypercalcemia. Despite greatly increased total weight of the parathyroid tissue (mean 1,509 mg), 34 patients had one to five normal-sized parathyroid glands. The incidence of such glands decreased with total gland weight. Nodular hyperplasia was found in 74% of the patients, and was characterized by considerable intraindividual size difference, while diffuse hyperplasia was associated with more moderate and symmetric glandular enlargement. During follow-up averaging 4.5 years, the incidence of persistent or recurrent hypercalcemia was slightly higher after subtotal than after total parathyroidectomy (11 and 11%, vs. 9 and 7%). Biochemical and/or radiologic signs of parathyroid bone disease were present in 36 (44%) of the patients before neck exploration and normalized postoperatively in all but seven. The outcome of parathyroid surgery thus was favorable in uremic patients with hypercalcemic hyperparathyroidism.     

Parathyroid surgery in patients with renal failure.

A subtotal parathyroidectomy was performed in 32 patients with hyperparathyroidism and renal dysfunction. Minimal long-term sequelae were observed [two patients with recurrent hyperparathyroidism (6.2%), one patient with persistent hypoparathyroidism (3.1%)]. This experience is compared with reports in the literature advocating total parathyroidectomy and autotransplantation. A subtotal parathyroidectomy remains the preferred approach at this institution. Patients with elevated alkaline phosphatase levels before surgery should be monitored carefully for early postoperative hypocalcemia. The low incidence (3.2%) of hyperparathyroidism observed in patients following successful renal transplantation indicates that hypercalcemic allograft recipients should be observed for at least 4 months before contemplating surgical intervention.     

Rapid onset intratubular calcification following renal transplantation requiring urgent parathyroidectomy

BACKGROUND: Secondary hyperparathyroidism is a common complication of end-stage renal disease often requiring parathyroidectomy. Renal transplant with the restoration of normal renal function often allows resolution of hyperparathyroidism, avoiding the need for parathyroid surgery. However, a proportion of patients with hyperparathyroidism become overtly hypercalcemic after renal transplantation which poses management dilemmas between medical and surgical treatment. CASE: We present the case of a 48-yearold man with end-stage renal failure known to have secondary hyperparathyroidism who received a living related renal transplant. Postoperatively he developed prompt hypercalcemia, polyuria, polydipsia and rapid onset intratubular calcification, leading to acute tubular necrosis diagnosed on renal biopsy on Day 7 post transplantation. He underwent surgical parathyroidectomy with resolution of his hypercalcemia and improved renal transplant function. DISCUSSION: This case emphasizes the need for good management of secondary hyperparathyroidism together with close surveillance of PTH in patients awaiting renal transplantation. With good renal transplant function hyperparathyroidism usually resolves. Posttransplant surgical parathyroidectomy should be reserved for severe progressive end organ damage.     

Drug Insight: renal indications of calcimimetics

Calcimimetics suppress the secretion of parathyroid hormone by sensitizing the parathyroid calcium receptor to serum calcium. Cinacalcet (Sensipar/Mimpara), Amgen Inc., Thousand Oaks, CA), the first-in-class calcimimetic agent approved for treatment of secondary hyperparathyroidism in dialysis patients, is, in association with higher dose of a calcium-based oral phosphate binder, a well-tolerated and effective alternative to standard treatments such as vitamin D derivatives in association with a non-calcium-based oral phosphate binder. Here, we present an overview of evidence in support of this assertion. We extend our discussion to encompass other indications for calcimimetics -- secondary hyperparathyroidism in predialysis chronic kidney disease patients, hypercalcemic hyperparathyroidism in renal transplant recipients, primary hyperparathyroidism, and hypercalcemia associated with parathyroid carcinoma -- as well as providing guidance on optimal usage of this drug.     

The problems encountered in the surgical management of primary hyperparathyroidism

The problems encountered in the diagnosis and treatment of primary hyperparathyroidism were studied in 69 cases. The accuracy of imaging for hyperplasia was less than that for adenoma or carcinoma and the major causes for multiple operations were a failure to locate the four glands and mediastinal adenoma. The intravenous administration of high doses of calcitonin could reduce the serum calcium level of patients in hypercalcemic crisis. Carcinoma required ipsilateral modified radical neck dissection because of lymph node metastases, and non-medullary thyroid carcinoma was often associated with primary hyperparathyroidism. We found removal of the parathyroid adenoma and biopsy or extirpation of only one macroscopically normal gland to be a fully satisfactory procedure after bilateral neck exploration and attempting to identify at least four glands.     

Normocalcemic hyperparathyroidism. Biochemical and symptom profiles before and after surgery.

Patients with normocalcemic hyperparathyroidism represent a diagnostic and therapeutic challenge. It is unclear to what extent these patients benefit from surgery in terms of correction of their serum chemistry abnormalities and their symptoms. We studied 142 patients: 23 with normocalcemic hyperparathyroidism (serum calcium levels below 2.62 mmol/L), 35 with intermittent hypercalcemia, and 84 with hypercalcemic hyperparathyroidism. Serum chemistry analyses and a standardized questionnaire of symptoms were completed before and after surgery. Overall, patients in the normocalcemic group reported a similar frequency of preoperative symptoms; had a similar reduction in postoperative symptoms; and had a similar normalization of serum calcium, parathormone, and phosphate levels as those in the two control groups. This study indicates that factors other than elevated serum calcium levels are in large part responsible for the symptoms of hyperparathyroidism and that these patients benefit from operation.     

The problems encountered in the surgical management of primary hyperparathyroidism.

The problems encountered in the diagnosis and treatment of primary hyperparathyroidism were studied in 69 cases. The accuracy of imaging for hyperplasia was less than that for adenoma or carcinoma and the major causes for multiple operations were a failure to locate the four glands and mediastinal adenoma. The intravenous administration of high doses of calcitonin could reduce the serum calcium level of patients in hypercalcemic crisis. Carcinoma required ipsilateral modified radical neck dissection because of lymph node metastases, and non-medullary thyroid carcinoma was often associated with primary hyperparathyroidism. We found removal of the parathyroid adenoma and biopsy or extirpation of only one macroscopically normal gland to be a fully satisfactory procedure after bilateral neck exploration and attempting to identify at least four glands.     

Hypercalcemic hyperparathyroidism and hypophosphatemic osteomalacia complicating neurofibromatosis

Summary Neurofibromatosis is sometimes complicated by impaired renal tubular reabsorption of phosphate, hypophosphatemia, and osteomalacia. Hyperparathyroidism has also been reported in patients with neurofibromatosis. When hypercalcemia and elevated levels of parathyroid hormone are found in osteomalacia, however, it may be difficult to determine if the hyperparathyroidism was primary or tertiary. We describe a patient with neurofibromatosis, hypercalcemic hyperparathyroidism, hypophosphatemic osteomalacia, vitamin D deficiency, and clear-cell hyperplasia of all four parathyroid glands. Serial biomechanical, bone biopsy, and densitometric studies confirmed that treatment with ergocalciferol, calcium, and phosphate supplements significantly improved the osteomalacia but caused increased parathyroid overactivity. After subtotal parathyroidectomy, the parathyroid hormone concentration became normal and the bone mineral content increased at the spine and hip, but inappropriate phosphaturia persisted. The findings indicate that hyperparathyroidism, osteomalacia, and vitamin D deficiency adversely affect each other.     

Familial Hyperparathyroidism without Multiple Endocrine Neoplasia

n = 4) or recurrent ( n = 3) hyperparathyroidism. Three patients (19%) also had papillary thyroid cancer, and 7 (44%) had other coexistent thyroid disorders. Among 51 patients with FHPT reported in the literature, 23 (45%) had serum calcium ≥ 3.75 mmol/L, and 23 (45%) had multiple abnormal parathyroid glands; 10 (20%) had recurrent hyperparathyroidism. FHPT without other endocrinopathies is a distinct entity. Patients with FHPT have multiple abnormal parathyroid glands and are prone to both recurrent and persistent hyperparathyroidism. They frequently present with profound hypercalcemia or hypercalcemic crisis, in contrast to patients with MEN-associated hyperparathyroidism or sporadic hyperparathyroidism.     

Hyperparathyroidism associated with renal disease. Pathogenesis, natural history, and surgical treatment

Hyperparathyroidism associated with renal failure is due to chronic parathyroid stimulation by hypocalcemia, which, in turn, results from hyperphosphatemia and low circulating 1,25(OH)2D3. If prophylactic measures and medical treatment of hyperparathyroidism fail, parathyroidectomy should be performed to prevent the progression of bone disease. Resolution of renal hyperparathyroidism is often seen after kidney transplantation, but some hypercalcemic patients require prophylactic or therapeutic parathyroidectomy. Hypocalcemia is the most common complication after parathyroidectomy. Our long-term results with subtotal parathyroidectomy are satisfactory. Total parathyroidectomy plus parathyroid autograft should be used in selected cases.     

Urinary excretion of parathyroid hormone-related protein fragments in patients with humoral hypercalcemia of malignancy and hypercalcemic tumor-bearing nude mice

To investigate whether parathyroid hormone-related protein (PTHrP), a hypercalcemia-inducing factor responsible for malignancy-associated hypercalcemia (MAH), is excreted into urine of these patients, radioimmunoassay was established using antiserum specific for the C-terminal region of PTHrP-(127-141). Immunoreactive PTHrP (iPTHrP) was detected in the urine of all patients with MAH (n = 6) in whom nephrogenous cyclic AMP excretion was elevated. However, iPTHrP was not detected in the urine of normal subjects (n = 25) or hypercalcemic patients with primary hyperparathyroidism (n = 8). In normocalcemic patients with malignant disorders iPTHrP was not detected in the urine in most cases (24 of 25 patients) but was detectable in 1 of 25 patients. iPTHrP was also detected in the urine of hypercalcemic nude mice transplanted with PTHrP-producing tumors, but not in the urine of control and normocalcemic nude mice transplanted with PTHrP-nonproducing tumor. Furthermore, size-exclusion high-performance liquid chromatography revealed that the molecular weight of iPTHrP is about 2000-6000 daltons in the urine of patients as well as tumor-bearing nude mice. These data indicate that the fragments of the C-terminal region of PTHrP are excreted into the urine of patients with MAH and in a few normocalcemic patients with malignancies, suggesting that the measurement of iPTHrP in the urine is potentially useful in the differential diagnosis of hypercalcemia, particularly in differentiating humoral hypercalcemia of malignancy and primary hyperparathyroidism.     

Grouping of patients with hyperparathyroidism by clinical signs, correlated to some biochemical findings.

Serum parathormone (S-PTH), total and free fractions of serum calcium (Cat and Caf), urinary excretion of cyclic 3',5'-adenosine monophosphate (cAMPu), serum phosphate and serum magnesium were analysed in 68 patients with hyperparathyroidism verified by operation and PAD. The diagnostic significance of the analyses was examined. It was shown that Caf was consistently above normal even in patients in whom the other tests were normal. The best diagnostic sensitivity was thus found for Caf followed by Cat, S-PTH and cAMPu. The results of these tests were generally correlated to each other except in patients with impaired renal function in whom S-PTH increased out of porportion to the other tests. Cat and Caf were significantly correlated to each other. However, Caf was pathologic even when Cat was normal. It is concluded that for hypercalcemic patients Cat and Caf are the most reliable tests. S-PTH is elevated only in some hypercalcemic patients. In normocalcemic patients all tests except Caf show normal values.