Mucin-producing parathyroid carcinoma.

A 67-year-old white male presented with symptomatic hypercalcemia (15.6 mg/dl) in December 1989. He had undergone thyroidectomy for removal of a mucin-producing adenocarcinoma of the thyroid in 1967, and after eight years of follow-up during which time no other neoplasms were detected, he was reported as a unique case of this syndrome. Mild hypercalcemia (less than 11.0 mg/dl) was first noted in 1987, and this had remained stable until shortly before the acute presentation. Multiple lung nodules were observed radiographically and presumed to be granulomatous until increased size was observed shortly before presentation. Serum intact PTH was 190 pg/ml (n 10-55), but at neck exploration no parathyroid tissue was found and surgery did not resolve the hypercalcemia. Serum PTHrP was undetectable. Biopsies from all three lobes of the right lung revealed numerous nodules of metastatic adenocarcinoma with cords of tumor cells surrounded by mucin. The histology was similar to that obtained 23 years earlier. Following left upper lobe resection with removal of a 3-cm nodule, hypercalcemia resolved. The tumor stained strongly positive with a peroxidase stain for PTH using a polyclonal antibody. Northern blot hybridization of total RNA from the tumor confirmed the presence of message for PTH but not PTHrP. The original diagnosis has been revised to that of a unique case of mucin-producing parathyroid cancer with an extraordinarily long latency period before recurrence.

Cushing's disease: dilemmas of diagnosis and management.

Determining the cause of Cushing's disease and correcting the abnormality presents a continuing challenge to the clinician despite remarkable advances in diagnostic and therapeutic techniques. We present seven cases to illustrate 1) the classic disorder cured by pituitary adenomectomy; 2) persistence of the disease after adenomectomy; 3) Cushing's disease manifesting in the puerperium and remitting with dopamine agonist therapy; 4) a patient whose disease relapsed at least five times during 20 years of treatment by adrenalectomy, pituitary radiation, mitotane, and pituitary adenomectomy; 5) the Nelson syndrome; 6) the ectopic adrenocorticotropic hormone (ACTH) syndrome in a patient with dexamethasone suppressible urinary cortisol who had a pituitary adenoma which stained positively for ACTH but who was not cured by total hypophysectomy; and 7) a patient whose ACTH-secreting tumor proved fatal despite repeated surgical, radiologic and pharmacologic measures.

Hypersecretion of growth hormone and prolactin in McCune-Albright syndrome.

Acromegaly and hyperprolactinemia have been reported in association with the McCune-Albright syndrome, but the pathophysiology of the GH and PRL hypersecretion that occurs in patients with this disorder has not been defined. We studied GH and PRL secretory dynamics in three patients with McCune-Albright syndrome and hypersecretion of these hormones. Each patient had excessive linear growth, glucose-non-suppressible plasma GH concentration, and GH responsiveness to TRH and GHRH. In response to exogenous GHRH, plasma GH concentrations rose approximately 2-fold in all three patients. Plasma GHRH levels were 20-40 ng/L (normal, less than 30). Study of the spontaneous GH secretory pattern in two patients indicated nocturnal augmentation of GH release. Bromocriptine therapy failed to reduce plasma GH in all patients; in one patient treatment with octreotide, a long-acting somatostatin analog, partially suppressed plasma GH and insulin-like growth factor I levels. These results suggest that hypersecretion of GH in the McCune-Albright syndrome is not due to ectopic GHRH production or autonomous somatotroph function. The results are similar to those described in classic acromegaly due to GH-secreting pituitary tumors. However, the lack of radiographic pituitary enlargement, the variable pituitary pathology reported in similar patients, and frequent concordance of GH and PRL excess suggest that the pathogenesis of this disorder may differ fundamentally from other forms of acromegaly or gigantism. The pathophysiology may reflect abnormal hypothalamic regulation and/or an embryological defect in pituitary cellular differentiation and function.

Acromegaly associated with a bronchial carcinoid tumor: evidence for ectopic production of growth hormone-releasing activity.

A patient with acromegaly, pituitary enlargement, and elevated plasma GH levels also had a bronchial carcinoid tumor. Signs and symptoms of active acromegaly along with elevated GH levels persisted for 11 yr after hypophysectomy and pituitary stalk section. Resection of the bronchial carcinoid reduced plasma GH to barely detectable levels. Extracts of the frozen carcinoid tumor were devoid of significant GH, but when added to isolated pituitary cells of estrogen-primed male rats in 4-day primary culture exhibited specific GH-releasing activity in vitro. These findings strongly suggest that the patient's acromegaly resulted from continual stimulation of pituitary somatotrophs by a GH-releasing factor secreted by the bronchial carcinoid.