Hypercalcemia is one of the most common metabolic disorders and it may be generated by many different pathologic conditions. The most common categories are malignancy, PHPT and vitamin D-induced hypercalcemia; the less frequent include drug-induced conditions (eg, lithium, thiazide diuretics), immobilization, tuberculosis, sarcoidosis and rhabdomyolysis.
Identifying disease etiology is very important, since, subsequent management differs according to pathology. Although a detailed personal and family history, physical examination, and laboratory analyses can differentiate the causes in most cases, hypercalcemia often remains a challenging condition for clinicians. PTH level is the classic discriminator between parathyroid disease-dependent hypercalcemia and others, whereas PTHrP is the most useful analytical method in HHM.
The most frequent cause of PHPT is a solitary adenoma composed mainly of chief cells producing PTH. In contrast, oxyphil adenoma meets the following criteria: 1) consists of at least 90% oxyphil cells; 2) histologically normal excision or biopsy of a second gland excluding the possibility of parathyroid hyperplasia; and 3) immediate postoperative normalization of hypercalcemia . In this reported case, all the criteria were met.
The literature review reports 142 cases of oxyphil parathyroid adenomas [8–10]. The ability of this histological form to secrete PTH has been demonstrated during the last 30 years  ; in fact, hypercalcemia was associated to secretion of PTH due to oxyphil adenomas in only 124 of 142 reported cases [8, 10, 11].
Since 1976, approximately 140 cases of hypercalcemia and normal PTH levels due to parathyroid adenoma have been reported in the literature [12–15] ; however, no correlation between the atypical biochemical presentation, histological features and causative factors has been demonstrated. In this regard, Hollemberg et al.  and Perez et al.  proposed the following theoretical explanations to the mechanism of inappropriately low PTH level in the PHPT cases observed: a circulating inhibitor of PTH; the pulsatile secretion of the hormone; an abnormal PTH molecule with increased biologic activity; increased peripheral tissue sensitivity to normal PTH; or the presence of another mediator of hypercalcemia (eg, PTHrP). None of these hypotheses have been verified. Lafferty et al.  emphasized that PHPT cannot always be ruled out because of a low-normal serum intact or biointact PTH and suggested that repeated PTH measurements after serum dilution in suspected cases of PHPT with low-normal PTH levels may be a useful method for detecting atypical forms of PTH.
PTHrP is a factor responsible for malignancies associated with hypercalcemia such as lung cancer, breast carcinoma, pancreatic endocrine tumors, renal cell carcinoma; esophageal squamosous cell carcinoma, pheochromocytoma and hematological neoplasia. PTHrP has been demonstrated in adult human parathyroid tissue under normal and pathological conditions; however, the role of this peptid secreted in 12 reported cases of oxyphil parathyroid adenoma associated with hypercalcemia has not yet been defined [9, 10]. In fact, in 11 cases, the PTH level has not been reported , and in one, hypercalcemia depended on simultaneous hypersecretion of PTH .
Nevertheless, these studies have established the correlation of PTHrP expression with the age-related metaplastic change of parathyroid cells into the oxyphil phenotype, through a paracrine/autocrine regulatory mechanism [9, 10].
To our knowledge, the association of immunohistochemical positivity for PTHrP-antigens with normal PTH levels, the immediate postoperative normalization of hypercalcemia, and the histological features of parathyroid adenoma have not been previously reported.
Moreover, technetium Tc-99m sestamibi imaging techniques have played a very important role in defining the preoperative localization in this case study. The predominance of oxyphil cells within an adenoma actually increases Tc-99m-sestamibi scan sensitivity in a statistically significant manner, since sestamibi uptake likely increases in more metabolically active lesions and when the preoperative calcium level is ≥ 9.5 mg/dL so as to reduce the risks of bilateral surgical neck exploration and persistent PHPT .