Pituitary prolactin-secreting macroadenoma combined with bilateral breast cancer in a 45-year-old male.

We describe an unusual case of bilateral breast cancer synchronous with pituitary macroprolactinoma in a young male. Up to date, only very few of such cases have been described worldwide and to our knowledge this is the first one in which both breast cancer and pituitary macroadenoma have been found together at the time of presentation. A 45-year-old male was diagnosed as having a pituitary macroprolactinoma and bilateral breast cancer on the basis of hypogonadism (testosterone 2.9 pmol/l) with very high levels of prolactin (33,100 U/l), typical neuroradiologic finding of a pituitary macroadenoma, marked bilateral gynecomastia with mammographic pattern highly suspected for cancer and subsequent hystological confirmation. Bilateral mastectomy was performed and medical therapy with bromocriptine 10 mg/day was started. After 2-year follow-up the patient is disease-free. Hormonal, neuroradiological and oncological patterns are all negative or markedly improved. We stress the importance of prolactin for its possible biological effects on breast cancer induction or growth. Moreover in any case of hyperprolactinemia we suggest a mammographic examination and, in the case of breast cancer, at least a baseline hormonal profile.

Pulmonary hyalinizing granuloma. A limited form of Wegener's granulomatosis?

Pulmonary hyalinizing granuloma is an uncommon disease that consists of slowly enlarging nodules in the pulmonary parenchyma. It occurs rarely: in fact, fewer than 70 case reports have been published in the past 20 years. It is important however in the differential diagnosis of lung diseases manifesting multiple pulmonary nodules. The etiology and pathogenesis of this disorder are unknown. Evidence suggests that the nodules could be the result of a chronic exaggerated immune response to infectious agents or to any other process in which antigen-antibody complexes are involved. More than 50% of the patients reported have evidence of autoimmune phenomena, e.g. positive antinuclear antibodies, a positive rheumatoid factor, or circulating immune complexes. The present report describes, for the first time, a case of pulmonary hyalinizing granuloma in which the patient had antineutrophil cytoplasmic autoantibodies with a granular cytoplasmatic pattern with typical central accentuation of fluorescence intensity and negative nuclei. The presence of antineutrophil cytoplasmic autoantibodies suggests that pulmonary hyalinizing granuloma could be regarded as a localized, non-evolving, form of Wegener's granulomatosis or a purely granulomatous Wegener's granulomatosis.

Pituitary resistance to thyroid hormones.

Pituitary thyroid hormone resistance (PRTH) refers to a particular form of thyroid hormone refractoriness that is accompanied by peripheral hyperthyroidism, as only the TSH-secreting pituitary cells appear to be resistant to the effects of thyroid hormones. The presence of PRTH is suspected and diagnosed on the basis of the finding of high free thyroid hormone levels along with unsuppressed TSH, clinical signs and symptoms of hyperthyroidism and values of at least one of the parameters evaluating peripheral thyroid hormone action in the hyperthyroid range. However, most patients with PRTH present with clinical signs and symptoms of thyroid dysfunction, particularly goiter and tachycardia, overlapping those recorded in patients with generalized thyroid hormone resistance (GRTH), i.e. refractoriness to thyroid hormones at both pituitary and peripheral tissue level. Moreover, most of them display normal values of other parameters evaluating the peripheral effects of thyroid hormones and bear mutations in the gene encoding for T3 nuclear receptors similar to those found in patients with GRTH. These findings are questioning the existence of PRTH as a separate clinical entity and support the view that the various forms of thyroid hormone resistance may be part of a spectrum of disease with variable expression in different issues.

Sex hormone-binding globulin measurement in patients with inappropriate secretion of thyrotropin (IST): evidence against selective pituitary thyroid hormone resistance in nonneoplastic IST.

The differential diagnosis of the various forms of inappropriate secretion of TSH (IST), i.e. generalized thyroid hormone resistance (GRTH), selective pituitary resistance [non-neoplastic IST (nnIST)], and tumoral pituitary TSH hypersecretion [neoplastic IST (nIST)], mainly rests on clinical observation, skull imaging, and measurement of several parameters assessing peripheral thyroid hormone effects. Clinically, patients with GRTH usually display compensated hypothyroidism, while those with nnIST or nIST are hyperthyroid. Since sex hormone-binding globulin (SHBG) measurement has been shown to be a reliable parameter in distinguishing between euthyroid and hyperthyroid states, we evaluated serum SHBG levels in 39 patients with IST (7 with GRTH, 15 with nnIST, and 17 with nIST). The results were compared to those in 68 normal subjects, 76 hyperthyroid patients, and 31 hypothyroid patients. SHBG levels in patients with either GRTH or nnIST were similar to those in controls or hypothyroid patients [GRTH, 40.5 +/- 11.8 (+/- SD) nmol/L (range, 26.4-57.5); nnIST, 29.7 +/- 12.8 nmol/L (range, 6.8-46.8); controls, 36.7 +/- 21.7 nmol/L (range, 5.4-96.5); hypothyroid, 30.8 +/- 14.4 nmol/L (range, 10.4-63.3)]. On the contrary, SHBG levels in patients with either overt hyperthyroidism or nIST were significantly higher than those in the above groups [hyperthyroid, 149 +/- 111 nmol/L (range, 48-557); nIST, 99.5 +/- 54.7 nmol/L (range, 21.6-259)]. The apparent overlap of SHBG values between hyperthyroid patients and controls almost completely disappeared when comparisons were made with control groups matched for age and sex. Additional indices of peripheral thyroid hormone action (basal metabolic rate, cardiac systolic time intervals, and Achilles' reflex time) were normal in patients with GRTH, while they were in the hyperthyroid range in patients with nnIST and nIST. After successful treatment of hyperthyroidism, SHBG levels normalized in patients with nIST, but they did not change in patients with nnIST. In conclusion, the measurement of SHBG in patients with IST is useful in differentiating the neoplastic form from that due to thyroid hormone resistance, but it fails to distinguish between generalized and pituitary resistance to thyroid hormone action. Moreover, the present data suggest that the resistance to thyroid hormone action in patients with nnIST is not selective at the thyrotroph cell level, but also involves the hepatic SHBG-synthesizing cells, thus supporting the view that the various forms of thyroid hormone resistance could represent a continuum of the same defect with variable expression in different tissues.