Ectopic cushing's syndrome caused by an 8 mm lung carcinoid localized by scintigram with the somatostatin analog111in-pentetreotide.

Small tumors producing adrenocorticophic hormone (ACTH) ectopically may be very difficult to locate. We describe a 57-year-old woman who presented with ectopic Cushing's syndrome as diagnosed by bilateral inferior petrosal sinus catheterization with corticotrophin-releasing hormone (CRH) test. Thoracic pentetreotide (a somatostatin analogue) revealed a small "hot spot" in the base of the left lung. This "hot spot" was constant throughout the procedure. A second thoracic CT scan with 3-mm cuts showed a small image in the area under suspicion, similar to vascular images found elsewhere in both lungs. At surgery, an 8-mm tumor was found and excised. Pathological examination revealed a carcinoid tumor immunoreactive for ACTH, beta-endorphin, bombesin, serotonin, and the α-subunit. One month after surgery, the patient was clinically well and had normal adrenal function. An111ln-pentetreotide scintiscan clearly identified a small ACTH-producing neuroendocrine tumor of the lung undetectable by plain chest radiography or CT scan.

Cytomegalovirus adrenalitis in acquired immunodeficiency syndrome.

Seventy-three adrenal glands of 44 patients with acquired immunodeficiency syndrome (AIDS) were examined and graded histologically to reveal cytomegaloviral (CMV) adrenalitis. The number of CMV inclusion bodies (IB) were evaluated and compared with 3 methods in 58 adrenal glands of 40 patients: histological sections, immunocytochemistry for early antigens of CMV, and in situ hybridization with biotinylated probes for CMV DNA All 73 adrenal glands contained foci of lymphocytic infiltrate. Forty (55%) showed CMV adrenalitis and necrosis, which were more extensive in the medulla than in the cortex. The number of CMV IB increased with the severity of necrosis and fibrosis (grades I, 1.0; II, 3.6; III, 27.8 IB/ thousand cells counted in 20 fields). More than 85 percent of both glands were necrotic in0 only I patient (2.3%). For the 3 methods, the means of the number of CMV IB were as follows: in situ hybridization with biotinylated probe, 17.7; immunocytochemistry, 12.9; and H&E, 8.1. However, using multivariant analysis, there was no statistically significant difference. Thirty-three (45%) adrenal glands contained no CMV IB by any of the 3 methods. We conclude that CMV adrenalitis is a common finding in patients with AIDS. Destruction of adrenal tissue is usually not widespread enough to result in adrenocortical insufficiency.

Hypothalamic neurocytoma with vasopressin immunoreactivity: Immunohistochemical and ultrastructural observations.

Hypothalamic tumors of neuronal derivation are rare. We describe the case of a 55-year-old woman with visual disturbances who was found by magnetic resonance imaging (MRI) to have a sellar and suprasellar tumor. She underwent subtotal surgical resection by a transsphe-noidal approach. By light microscopy the tumor displayed a uniform population of short spindle cells with round to oval nuclei, separated by an abundant fibrillary stroma containing axonal processes as shown by the Bodian stain. The neoplastic cells were immunoreactive for neuron-specific enolase (NSE), synaptophysin, and vasopressin, and nonimmunoreactive for glial fibrillary acidic protein (GFAP), vasoactive intestinal peptide (VIP), bombesin, chromogranin, neurofilament, cytokeratins (high and low molecular weight), vimentin, S100 protein, somatostatin, ß-endorphin, galactosamine, growth hormone-releasing hormone (GRH), neurophysin, serotonin, adrenaline and noradrenaline, and corticotropin-releasing hormone (CRH). Ultrastructural features included an abundance of neurosecretory granules within neurites and perinuclear cytoplasm. Synapses and glial stroma were not demonstrable. The term hypothalamic neurocytoma delineates this neuronal tumor with distinctive histologic, immunohistochemical, and ultrastructural features. The identification of vasopressin within the tumor provides evidence of neuroendocrine function.

Absence of somatotrophs, lactotrophs, and thyrotrophs in the pituitary of two dwarfs with hypothyroidism: Deficiency of pituitary transcription factor-1?

Most patients with dwarfism due to growth hormone (GH) deficiency have normal pituitary somatotroph morphology and GH response to GH-releasing hormone (GRH), consistent with decreased GRH synthesis, release, or delivery. Primary pituitary hyposecretion of GH may result from adenohypophysial tissue destruction caused by tumors, such as craniopharyngioma. We report a hitherto undescribed form of primary pituitary dwarfism associated with absence of adenohypophysial GH, prolactin (PRL), and thyrotropin (TSH). Two sisters had dwarfism, hypothyroidism, and hypoglycemia. The first child had craniofacial abnormalities and died at age 11/2 months of fluid overload. The second sibling died at age 4 years of pulmonary congestion. At autopsy, both pituitaries were small and acidophils were conspicuously absent. They contained a normal number of corticotrophs with intense adrenocorticotropin (ACTH) immunoreactivity, and gonadotrophs with normal content of α-subunit and ß-subunits of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). No GH, PRL, or ß-TSH immunoreactivity was identified. The thyroid glandswere atrophic. Both children had marked pancreatic nesidioblastosis, with an increased number of insulin-containing cells. This clinicopathologic entity appears to represent a familial disorder in which there is defective development of three adenohypophysial cell types: somatotrophs, lactotrophs, and thyrotrophs. A common pituitary transcription factor, Pit-1, has been implicated in the differentiation of these three cell types. The pituitary changes in these two children resemble those described in Snell, Jackson, and Ames dwarf mice, which have recently been shown to be due to abnormalities of the Pit-1 gene. We suggest that this novel human disease is due to deficient or abnormal pituitary transcription factor Pit-1.

Histological, immunohistochemical, and ultrastructural features of a rat medullary thyroid carcinoma transfected with a corticotropin-releasing hormone cDNA expression vector.

Clonal cell lines producing corticotropin-releasing hormone (CRH) have been generated by transfection of the W2 rat medullary thyroid carcinoma (MTC) cell with a CRH-encoding CMV/ SV40 expression vector. Here, we report the morphological, immunohistochemical, and ultrastructural features of rat tumors derived by implantation of CRH-producing W2CRH-7 cells and compare them with non-CRH-producing W2 MTCs. Both types of tumors grew rapidly and consisted of sheets and nests of pleomorphic cells infiltrating adjacent adipose tissue. Immunohistochemistry revealed CRH in only W2CRH-7 tumors; scattered cells in these tumors also were immunoreactive for chromogranin and for vasoactive intestinal peptide. Otherwise, the two tumor types exhibited similar profiles of various neuroendocrine markers, including neuron-specific enolase, synaptophysin, calcitonin, and somatostatin. Ultrastructurally, the tumors contained abundant dilated rough endoplasmic reticulum, a prominent Golgi apparatus, and numerous lysosomes. Very few secretory granules were noted in the W2 tumors; by contrast, secretory granules, although still not numerous in the majority of W2CRH-7 cells, were more abundant in scattered cells of those tumors. The positive immunostaining for CRH is consistent with the observations of increased plasma CRH and pituitary-adrenal activation induced by these transplanted tumors. This system provides a valuable model for CRH excess mimicking tumoral CRH-dependent Cushing's syndrome in human patients.

Medullary carcinoma of the thyroid with metastasis to the pituitary gland.

A case of metastatic medullary thyroid carcinoma presenting with anterior pituitary dysfunction is reported. Initial evaluation revealed an intrasellar mass at a time when serum calcitonin and carcinoembryonic antigen levels were elevated, and histological analysis of resected tissue demonstrated the presence of metastatic medullary carcinoma of the thyroid. Immunohis-tochemical analysis confirmed the presence of calcitonin in the tumor cells. Like other malignant processes, metastatic medullary carcinoma of the thyroid may involve the pituitary gland and should be included in the differential diagnosis in the appropriate clinical setting.