Tumor-induced Osteomalacia: A Sherlock Holmes Approach to Diagnosis and Management.

Tumor-induced osteomalacia (TIO) is a subtype of paraneoplastic syndrome associated with hypophosphatemia due to renal phosphate wasting in adults. The humoral factor responsible for clinical picture known as fibroblast growth factor 23 (FGF23) is most often secreted by benign yet elusive mesenchymal tumors, difficult to localize, access, and excise completely; rarely, they are multiple and malignant. Paradoxical inappropriately normal or low levels of 1,25-dihydroxyvitamin D in the setting of hypophosphatemia is due to suppressive effect of FGF23. The following case report describes a 31-year-old male with symptoms of multiple fractures and severe muscle weakness, hypophosphatemia with elevated tubular maximum reabsorption of phosphate/glomerular filtration rate with low active Vitamin D, prompted assay for C-terminal FGF23, which was elevated multifold. The tumor was localized with whole body 68-Gadolinium DOTANOC positron emission tomography-computed tomography fusion scan in the left nasal cavity with ipsilateral maxillary antrum. It was excised through transnasal approach and found to be mesenchymal tumor on histopathology. At 1 week of follow-up, serum phosphate became normalized without supplementation. The patient is in follow-up for further measurement of FGF23 level and signs of recurrence. Because the occurrence of such a condition is rare and most often misdiagnosed or mismanaged for years, it is important to recognize this condition in differential diagnosis as potential curative surgical option is a reality.

Prolactin and cancer: Has the orphan finally found a home?

Prolactin has, for long, been associated with galactorrhea and infertility in women while its role in men is largely unknown. Recently, expression of prolactin in various other tissues like the breast, prostate, decidua, and the brain has been recognized. This has led to evaluation of paracrine and autocrine actions of prolactin at these tissues and a possible role in development of various cancers. Increased expression of PRL receptors has also been implicated in carcinogenesis. Breast cancer has the strongest association with increased prolactin and prolactin receptor levels. Prostate cancer also has reported significant association, while the role of prolactin in colorectal, gynecological, laryngeal, and hepatocellular cancers is more tenuous. Prolactin/prolactin receptor pathway has also been implicated in development of resistance to chemotherapy. Thus, the effects of this pathway in carcinogenesis seem widespread. At the same time, they also offer an exciting new approach to hormonal manipulation of cancers, especially the treatment-resistant cancers.

Anaemia and marrow fibrosis in patients with primary hyperparathyroidism before and after curative parathyroidectomy.

OBJECTIVE: To determine the relationship between anaemia and myelofibrosis in patients with symptomatic primary hyperparathyroidism (PHPT) and to assess the effect of curative parathyroidectomy on anaemia and marrow fibrosis. DESIGN AND METHODS: In this prospective follow-up study of 28 consecutive patients with symptomatic PHPT from January 2005 to June 2006, 15 patients were diagnosed with anaemia (haemoglobin < 130 g/l in males and < 120 g/l in females), eight (53%) of whom were finally recruited for the study. Complete blood cell count, serum calcium, phosphorus, alkaline phosphatase, intact PTH and 25-hydroxyvitamin D and bone marrow examination were performed both before and after parathyroidectomy in all (n = 8) patients, but bone marrow examination after surgery was performed only in those who had marrow fibrosis at baseline (n = 6). RESULTS: Anaemia was observed in 15 (53.3%) of the 28 patients with symptomatic PHPT. Normocytic normochromic anaemia that is characteristic of PHPT was found in 14 (50%) patients. Eight of the 15 patients with anaemia had a bone marrow examination and marrow fibrosis was observed in six (75%). Both anaemia and marrow fibrosis improved after successful parathyroidectomy, but improvement in anaemia was significant (P = 0.02) only in those with marrow fibrosis at baseline. Marrow fibrosis did not correlate with duration of the disease (P = 0.17), degree of hypercalcaemia (P = 0.53) or serum levels of intact PTH (P = 0.60). CONCLUSIONS: Anaemia is common in patients with symptomatic PHPT, and was associated with marrow fibrosis in the majority of the patients who underwent bone biopsy. Both anaemia and marrow fibrosis improved after curative parathyroidectomy, but improvement in anaemia was noticeable only in those who had marrow fibrosis at presentation.

Very low or undetectable intact parathyroid hormone levels in patients with surgically verified parathyroid adenomas.

OBJECTIVES: To report and explore potential reasons for undetectable or low-normal serum intact PTH levels in patients with surgically verified primary hyperparathyroidism with parathyroid adenomas, review the relevant literature, and offer suggestions for management of such patients occasionally encountered in clinical practice. For future research, to help understand mechanisms underlying 'undetectable' or inappropriately low serum intact PTH levels. METHODS: Serum intact PTH levels were measured pre- and postoperatively by immunochemiluminescent assay (ICMA) and the results were confirmed by at least two repeated measurements on different occasions in each patient. PATIENTS: We encountered two unusual patients with primary hyperparathyroidism who had suggestive biochemical and/or clinical features of primary hyperparathyroidism. However, serum intact PTH levels were either very low or undetectable in the context of hypercalcaemia, with no other obvious cause. A (99m)Tc sestamibi scan showed increased uptake in one of the parathyroid glands, suggesting a single adenoma in each case that was confirmed at surgery. RESULTS: In the first patient, from India, mean +/- SD serum calcium was 2.6 +/- 0.32 mmol/l (reference range 2.12-2.74 mmol/l) with intact PTH of 0.11 pmol/l (reference range 1.1-7.59 pmol/l). In the second patient, from the USA, mean +/- SD serum calcium and intact PTH were 2.9 +/- 0.07 mmol/l (reference range 2.17-2.51 mmol/l) and 1.35 pmol/l (reference range 1.1-7.59 pmol/l), respectively. Following curative parathyroidectomy, serum calcium levels normalized in both patients. By contrast, serum intact PTH levels, which were either suppressed or very low before surgery, rose into the low-normal reference range in all patients. CONCLUSIONS: When the clinical suspicion is high, the diagnosis of primary hyperparathyroidism should be pursued despite suppressed or low-normal serum intact PTH levels after carefully excluding other causes of hypercalcaemia. Further research on various intact PTH molecular species secreted by parathyroid adenomas or post-translational changes in the intact PTH molecule that might interfere with in vitro measurements should be undertaken to understand the precise reason(s) for such anomalous findings.

Characteristics of primary hyperparathyroidism in adolescents.

AIM: To analyze adolescent primary hyperparathyroidism (PHPT) in India. DESIGN: A retrospective analysis of consecutive medical records of patients with PHPT < or =20 years old who underwent parathyroid surgery at a tertiary care center in north India from 1993 to 2006. METHODS: Fourteen adolescents underwent clinical, biochemical, hormonal, radiological and scintigraphic evaluation for confirmation of PHPT followed by parathyroidectomy. RESULTS: Mean (+/- SD) age of these patients was 15 +/- 3.9 years (8 female). All were symptomatic at presentation except one who had multiglandular involvement as a part of multiple endocrine neoplasia (MEN)-I screening. The common presenting manifestations included bone disease, recurrent nephrolithiasis and pancreatitis. Hypercalcemia was observed in eight of these patients. The mean (+/- SD) serum intact parathyroid hormone was 781 +/- 586 pg/ml. Ultrasonography localized an abnormal parathyroid gland in 12 (92%) of 14 patients, while 99mTc sestamibi scan (performed in 7) localized abnormal parathyroid glands in all (100%). All patients underwent bilateral neck exploration except one with MEN-I, who refused surgery. Twelve patients had single parathyroid adenoma and one had four-gland hyperplasia. Mean follow up was 44.1 months and none showed recurrence. CONCLUSIONS: Children and adolescents with pathological fractures with features of rickets, recurrent urolithiasis and pancreatitis should be screened for PHPT. Surgery is the treatment of choice.