Hypercalcemia associated with squamous cell carcinoma of tongue.

OBJECTIVE: To present a case and to review the relationship between tumor production of parathyroid hormone-related protein (PTHrP) and hypercalcemia in oral squamous cell carcinoma (SCC), with emphasis on tongue cancer. METHODS: We describe a patient with advanced, locally invasive SCC of the tongue in whom hypercalcemia developed as a result of PTHrP production by the tumor. In addition, the medical literature regarding PTHrP and hypercalcemia associated with malignant disease is reviewed. RESULTS: A 65-year-old man, who was admitted to the hospital because of one episode of unresponsiveness, was found to have a large, necrotic, ulcerated lesion overlying the left mandibular area. After biopsy of the tumor and total body imaging, he was diagnosed with advanced, locally invasive, poorly differentiated SCC of the tongue, stage T4 N1 M0. On admission, the serum calcium concentration was 12.5 mg/dL (normal range, 8.5 to 10.7), and the serum albumin level was 2.2 g/dL (normal range, 3.5 to 5.5). The serum intact parathyroid hormone level was 26 pg/mL (normal range, 10 to 65); the PTHrP level was 13.1 pmol/L (normal, <1.3). Hypercalcemia attributable to production of PTHrP by the tongue SCC was diagnosed. Initial treatment of the hypercalcemia with vigorous hydration yielded a limited response. Intravenous administration of pamidronate initially decreased the serum calcium level to 5.2 mg/dL, but then it progressively increased to 8.6 mg/dL during the next 4 weeks. The patient refused further treatment and died after 1 month. CONCLUSION: To our knowledge, this is the first case of hypercalcemia associated with SCC of the tongue in which the serum PTHrP level was measured and reported to be high. It should be measured in other similar cases.

Ectopic primary hyperparathyroidism.

OBJECTIVE: To review an unusual case of ectopic primary hyperparathyroidism. METHODS: We present a case report, including longitudinal results of laboratory studies, and comment on the difficulties with standard imaging techniques, interpretation of parathyroid pathologic findings, and use of invasive localization techniques. RESULTS: A 74-year-old woman underwent repeated assessments because of hypercalcemia. When standard parathyroid 99mTc sestamibi imaging was negative for adenoma and initial surgical exploration of the neck and removal of 3' parathyroid glands were unsuccessful in correcting the hyperparathyroidism, the ectopic adenoma was ultimately localized on an extended-field 99mTc sestamibi scan in the region of the right dome of the diaphragm. The localization was confirmed by selective venous sampling and angiography. The ectopic parathyroid adenoma was embolized, and 1 month later, the serum calcium level was normal. CONCLUSION: Ectopic lesions should be considered when standard imaging techniques are nonrevealing and standard neck exploration fails to disclose a parathyroid adenoma in a patient with persistent hypercalcemia. Selective venous sampling and angiography can assist in localization of ectopic parathyroid adenomas.

Anticardiolipin antibodies in Hashimoto's disease.

OBJECTIVE: To ascertain the presence and significance of anticardiolipin antibodies in patients with Hashimoto's disease. METHODS: We studied 19 patients (15 women and 4 men; age range, 26 to 79 years) with Hashimoto's disease. IgA, IgG, and IgM anticardiolipin antibodies were measured by enzyme-linked immunosorbent assay. RESULTS: Of the 19 study patients, 4 (21%) tested positive for anticardiolipin antibodies (IgG in 2 and IgM in 2). Patients with anticardiolipin antibodies did not exhibit a higher titer of antithyroglobulin or anti-thyroid peroxidase antibodies in comparison with patients without anticardiolipin antibodies. Moreover, no relationship was found between anticardiolipin antibody levels and thyroid hormone replacement therapy. None of the patients with high levels of IgG or IgM anticardiolipin antibodies had clinical features of the antiphospholipid syndrome. CONCLUSION: Our results showed an increased incidence of anticardiolipin antibodies in patients with Hashimoto's disease. The presence of these antibodies may be a nonspecific marker of activation of the immune system.

Abnormal results of liver function tests in patients with Graves' disease.

OBJECTIVE: To determine the frequency of liver dysfunction in patients with hyperthyroidism. METHODS: We analyzed the clinical records of 30 consecutive patients with Graves' disease to identify the spectrum of abnormal results of liver function tests. The values for alkaline phosphatase (AP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma -glutamyltransferase (GGT), and total bilirubin were examined. RESULTS: The frequencies of increased levels of AP, AST, ALT, GGT, and bilirubin in the current study group were similar to but somewhat lower than those reported in previous studies. Of the 30 study patients, 11 (37%) had at least one abnormal result of a liver function test. All 30 patients in the study had determinations of AP (not fractionated), of which 10 values (33%) were above normal (range, 124 to 283 U/L). Of the 30 patients who had determinations of AST, 5 (17%) had increased values that ranged from 36 to 71 U/L. Six of the 23 patients (26%) with determinations of ALT had increased values that ranged from 45 to 157 U/L. Of the 25 patients who had measurements of GGT, 6 had above normal results (range, 69 to 331 U/L). In addition, 2 of the 24 patients (8%) with determinations of total bilirubin had increased levels. CONCLUSION: These findings indicate that abnormal results of liver function tests are common in patients with hyperthyroidism and make the diagnosis of concomitant, unrelated liver disease difficult until the euthyroid state has been established.

Successful therapy for a mixed thyrotropin-and prolactin-secreting pituitary macroadenoma with cabergoline.

OBJECTIVE: To describe the first case of a mixed thyrotropin (TSH)- and prolactin-secreting pituitary macroadenoma that responded to therapy with cabergoline. METHODS: We present a case report with clinical, laboratory, and radiologic details. RESULTS: An 84-year-old woman with central hyperthyroidism due to a mixed TSH- and prolactin-secreting pituitary macroadenoma was successfully treated with orally administered cabergoline, 0.25 mg twice per week. Serial assays of thyroid and pituitary hormones were done, and magnetic resonance imaging of the pituitary was performed before and 16 weeks after initiation of cabergoline therapy. The patient had complete resolution of the increased pituitary hormone indices within 6 weeks after implementation of therapy, and these results were sustained for more than 16 weeks. A magnetic resonance imaging scan showed no change in tumor size at 16 weeks of therapy. CONCLUSION: When medical treatment of TSH-secreting tumors is considered, choices of efficacious drugs are limited. To our knowledge, this report describes the first case of a long-acting dopamine agonist used successfully to control hypersecretion of a mixed TSH- and prolactin-secreting macroadenoma. Oral administration of cabergoline twice a week was effective, convenient, and well tolerated. Further evaluation of cabergoline, when indicated as medical therapy for TSH-secreting tumors, is warranted.

Assessment of adrenal glucocorticoid function. Which tests are appropriate for screening?

The rapid cosyntropin stimulation test offers a simple means for detecting adrenal insufficiency. In contrast, assessment of suspected hypercortisolism (Cushing's syndrome) is difficult because cortisol levels fluctuate with intermittent release of corticotropin from the pituitary or from tumors. Also, a number of medications affect cortisol levels, leading to false-positive or false-negative results. The classic low-dose followed by high-dose dexamethasone test is cumbersome, and other, simpler studies, such as the overnight high-dose dexamethasone suppression test, may prove more practical and cost-effective. With both high and low levels of adrenal glucocorticoids, awareness and early recognition of the symptoms are important. An endocrinologist should be consulted when the overnight dexamethasone suppression test or the 24-hour urine cortisol collection is abnormal or if clinical suspicion is high despite normal results on screening tests.

Testosterone concentrations and oligomenorrhea in women with acne.

BACKGROUND: Androgen excess is frequently associated with oligomenorrhea as well as acne. Oligomenorrhea in hirsute women has been demonstrated to be associated with higher active testosterone levels than found in eumenorrheic hirsute women. This study was designed to evaluate whether similar findings are present in women with acne. Forty-four consecutive women with acne were evaluated by measuring their levels of total testosterone, biologically active testosterone, and free testosterone. The women with oligomenorrhea and acne had significantly higher levels of biologically active testosterone than those with eumenorrhea and acne. This implies that biological active testosterone should be measured in oligomenorrheic women with acne and, if elevated, consideration should be given to antiandrogen therapy. METHODS: Data were collected from 44 consecutive Caucasian women aged 14 to 38 years. The patients were separated into two groups based on menstrual history. Group 1 had regular menses, and group 2 had oligomenorrhea, defined as menstrual intervals of greater than 36 days. All patients had blood samples drawn on their initial office visit, regardless of the phase of the menstrual cycle, and the levels of total testosterone (TT), biologically active testosterone (BT), and free testosterone (FT) were obtained. RESULTS: The serum TT level was 87 +/- 41.3 ng/dL (range, 31-150 ng/dL) in oligomenorrheic women and 56 +/- 27.5 ng/dL (range 8-107 ng/dL) in eumenorrheic women. There was no statistically significant difference. The serum BT level in oligomenorrheic women was 33 +/- 16.9 ng/dL (range, 11-51 ng/dL) and in eumenorrheic women 19 +/- 13.6 ng/dL (range, 11-51 ng/dL). This difference was statistically significant (p < 0.05). The serum FT level in oligomenorrheic women was 18 +/- 9.4 pg/mL (range, 1-29 pg/mL) and in eumenorrheic women 10 +/- 7.1 pg/mL (range, 1-32 pg/mL). This difference was not statistically significant (Table 1). CONCLUSIONS: Women with acne and oligomenorrhea, similar to women with hirsutism and oligomenorrhea, have higher levels of biologically active testosterone than those with normal menses.

Finasteride for benign prostatic hyperplasia.

The pathogenesis of benign prostatic hyperplasia is related to the action of 5 alpha-dihydrotestosterone (DHT), the physiologically active form of testosterone. The conversion of testosterone to DHT is catalyzed intracellularly in prostatic tissue by the enzyme 5 alpha-reductase. Finasteride blocks the action of 5 alpha-reductase by competitively inhibiting the binding of testosterone to 5 alpha-reductase. The maximum effect of finasteride on reducing prostatic volume occurs after three months of oral therapy. Most patients experience improvement in urine flow rates, and side effects are minimal. However, following discontinuation of treatment, serum DHT levels return to baseline within two weeks.