Unusual presentation of primary hyperparathyroidism with osteoporosis, hypercalcemia, and normal parathyroid hormone level.

We report the case of a woman with osteoporosis, chronic hypercalcemia, and normal levels of parathyroid hormone (PTH). Surgical exploration revealed hyperplasia of the parathyroid glands. Hypercalcemia was corrected immediately by surgery, and this was followed by a dramatic improvement in bone mineral density. This case represents a rarely reported presentation of primary hyperparathyroidism with an atypical laboratory finding.

Hot flushes in men with pituitary adenoma.

BACKGROUND: Hot flushes are common in menopausal women and also in men made acutely hypogonadal after orchiectomy or testicular injury. It is, however, an unusual symptom in patients with hypogonadism secondary to pituitary tumors. METHODS: In evaluating the histories of men with hypogonadal state associated with nonfunctioning pituitary macroadenoma we were struck by the presence of hot flushes in four of them. RESULTS: All four of the patients were hypogonadal with sexual dysfunction preoperatively. All had low gonadotropins and low testosterone levels with varying degrees of panhypopituitarism. All had successful transsphenoidal removal of tumors. None had endocrine improvement following surgery. All patients had improvement in sexual function and the hot flushes with administration of testosterone postoperatively. CONCLUSIONS: Hot flushes are an uncommon presentation in men with pituitary adenoma. Perhaps the symptom will become more prominent if it is specifically questioned. We postulate that the cause of the flushing is related to nonsuppressed pulsatile secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus.

A naturally occurring mutation of insulin receptor alanine 1134 impairs tyrosine kinase function and is associated with dominantly inherited insulin resistance.

We have identified a previously undescribed genetic variant of the insulin receptor (Ala1134----Thr1134) in a family with the Type A syndrome of insulin resistance. Using the polymerase chain reaction to amplify insulin receptor cDNA and genomic DNA (exon 19), this mutation was detected in 1/2 alleles in the proband, her two affected sisters, and her affected father. Two normal alleles were present in the unaffected mother. No additional structural changes were encoded by the remainder of the proband's receptor cDNA. The Ala1134 mutant receptor was expressed in Chinese hamster ovary cells. The expressed mutant receptors were processed normally and displayed normal affinity of insulin binding but were markedly deficient in insulin-stimulated autophosphorylation. The mutant receptor was unable to catalyze the phosphorylation of the endogenous substrate, pp185, and insulin-stimulated kinase activity toward an exogenous substrate in vitro also was markedly impaired. Ala1134 is a highly conserved residue located in a consensus sequence found in most tyrosine kinases. It is likely that this previously uncharacterized residue and/or the immediate region surrounding it are important for normal kinase function in other members of this receptor family. This study also demonstrates that severe insulin resistance with dominant inheritance may be caused by a missense mutation in one allele of the insulin receptor gene.

Adrenocortical carcinoma.

In reviewing the experience of a number of authors and investigators, it is clear that early diagnosis of adrenocortical carcinoma is essential for cure. Of all the modalities of therapy currently available, surgical resection holds the most promise for cure or prolonged survival. Treatment for extensive local disease or metastatic disease has been discouraging, and the prognosis for reasonable, comfortable survival is poor. Unfortunately, the toxicity of mitotane, an adrenolytic agent and currently the most effective drug available, is often unacceptable and may militate against its use. Because many of the debilitating side effects of these tumors are related to hormone production, newer drugs that result in hormonal blockade may add considerably to the comfort of the patient. The development of less toxic chemotherapeutic agents presents a challenge for both the oncologist and the endocrinologist.

Adrenalectomy-oophorectomy and combined chemotherapy for carcinoma of the breast with metastases.

Thirty-one patients with carcinoma of the breast with metastases were treated by adrenalectomy-oophorectomy and randomized either for combined chemotherapy, vincristine, fluorouracil, methotrexate and thiotepa, beginning within one week after operation and continuing for three months or no chemotherapy. Statistical analyses were Gehan's modification of the Wilcoxon test for censored data, chi-square tests and life table analysis. Pretreatment characteristics--menopausal status, age, disease-free interval, prior hormone treatment and sites of metastases--of both groups were similar. Objective response occurred in 73 per cent of 11 patients in the treatment. A group compared with 47 per cent of 15 patients in the treatment B group, p greater than 0.50. Median duration to relapse in responders was 16 months in the treatment A group and 15 months in the treatment B group, p greater than 0.50. Median survival was 19 months in the treatment A group and 20 months in the treatment B group, p greater than 0.50. Results were not significant, and inclusion of five patients with less than three months of treatment, did not alter the results. Hence, the group receiving early symptomatic treatment did not show an improved response rate, improved duration of remission or enhanced survival time from ablative treatment.

Carcinomatous versus radiation-induced brachial plexus neuropathy in breast cancer.

A retrospective study was performed of 18 women in whom ipsilateral brachial plexus neuropathy developed after treatment for carcinoma of the breast. In the absence of metastatic tumor elsewhere, the only distinguishing feature between carcinomatous neuropathy and radiation-induced neuropathy was the symptom-free interval after mastectomy and radiation therapy. Women with an interval of less than a year have radiation-induced neuropathy. Brachial plexus exploration in difficult diagnostic situations will permit early treatment and avoid debilitating loss of function. Brachial plexus exploration for biopsy is safe and free of complications if performed carefully. Treatment of carcinomatous neuropathy is most likely to succeed if the tumor is hormonally sensitive, but radiotherapy may also be effective. Treatment of radiation-induced neuropathy remains largely ineffective.

Rebound response after estrogen therapy for metastatic breast cancer.

The estrogen rebound response in metastatic breast cancer has been reported in the past as a rare and short-lived phenomenon, not clearly associated with any aspect of the patient's clinical profile. In this series, 25% of patients responding to estrogen therapy had a further response when they no longer received the hormone. The median duration of this palliation was a minimum of 18 months and was similar to that of the initial estrogen response. Patients with a rebound response had significantly longer disease-free intervals before estrogen therapy and estrogen remissions than those who did not have a rebound response. These clinical factors may, therefore, be helpful in predicting the chances of a rebound response in any given patient. It is urged that patients be observed for objective improvement without therapy upon escape from estrogen palliation. Further palliative therapy should not be offered until definite progression of disease has been documented after any rebound response that occurs.

Syndromes resulting from ectopic hormone-producing tumors.

Among the malignant tumors of nonendocrine origin that are capable of producing polypeptide hormones and of manifesting as different endocrine syndromes discussed here are ectopic ACTH syndrome, SIADH, and ectopic gonadotropin-producing tumors.

A multidisciplined approach for the treatment of metastatic carcinoma of the breast.

We have reviewed our experience in a multidisciplined breast cancer clinic where we have utilized hormonal, ablative, and chemotherapetuci modalities. Our experience seesm to be similar to that of other groups in that oophorectomy treatment produces approximately a 61 per cent response (regression and arrest) rate, androgen therapy produces a 47 per cent response (regression and arrest) rate estrogen therapy produces a 40 per cent response (regression and arrest) rate, and ablative treatment produces approximately a 50 per cent response (regression and arrest) rate. Adrenalectomy and hypophysectomy showed similar response rates. Until it can be shown that hypophysectomy clearly offers enhanced benefits, this will not be utilized by our group except in those patients who cannot tolerate abdominal surgery (that is, patients with poor pulmonary reserve). Of interest is the high response rate (65 per cent) to ablative treatment in patients in whom disease exacerbates on additive hormonal treatment, with an increased duration of response and survival. Survival is increased in patients who are rebound responders after estrogen withdrawal. We expect to report data with future follow-up of this group of patients. New protocols will be instituted after review of the data in the hope of increasing clinical benefit and survival in this group of patients. Carcinoma of the breast accounts for almost 90,000 new cases of cancer a year, with metastases eventually developing in at least half of these patients. All physicians must be aware of the many complex problems associated with this disease and, hopefully, arrive at a logical approach for its control. We believe this can be achieved with a multidisciplined group approach as established at the Lahey Clinic Foundation.