Thyroid cancer is the most common cancer associated with acromegaly.

The aim of the study was to screen the malignancy in an acromegalic patient group and to determine whether there was any increased risk and the incidence of malignancy and its association with disease characteristics such as duration of disease, latency in diagnosis, and GH and IGF-1 levels. One hundred-five (65 female, 40 male) patients with acromegaly followed and treated at Cerrahpasa Medical School, Endocrinology and Metabolism outpatient clinic between 1983 and 2007 were included in this study. The patients were screened with colonoscopy, mammography, and thyroid and prostate ultrasonography (US). Malignancy was detected in 16 (15%) patients. Thyroid cancer was found in 5 patients (4.7%), breast cancer in 3 (2.8%), colon cancer in 2 (1.9%), lung cancer in 2 (1.9%), cervix cancer in 1 (0.9%), myelodysplastic syndrome (MDS) in 1 (0.9%), cholangiocarcinoma in 1 (0.9%), and multiple endocrine neoplasm (MEN) type 1 in 1 patient (0.9%). Cancer was more common in the male patients (P = 0.046) and high levels of GH increased the risk of cancer development (P = 0.046). In this series, the most commonly detected cancer types were thyroid followed by breast and colon cancers. Although high levels of initial GH seemed to increase the risk of cancer development in acromegalic patients, age, gender, age at the time of diagnosis, duration of disease, and initial IGF-I levels were not associated with cancer development.

Mechanisms for pituitary tumorigenesis: the plastic pituitary.

The anterior pituitary gland integrates the repertoire of hormonal signals controlling thyroid, adrenal, reproductive, and growth functions. The gland responds to complex central and peripheral signals by trophic hormone secretion and by undergoing reversible plastic changes in cell growth leading to hyperplasia, involution, or benign adenomas arising from functional pituitary cells. Discussed herein are the mechanisms underlying hereditary pituitary hypoplasia, reversible pituitary hyperplasia, excess hormone production, and tumor initiation and promotion associated with normal and abnormal pituitary differentiation in health and disease.

What is the link between nonlocalizing sestamibi scans, multigland disease, and persistent hypercalcemia? A study of 401 consecutive patients undergoing parathyroidectomy.

BACKGROUND: We hypothesized that nonlocalizing sestamibi scans would correlate with multigland disease and persistent primary hyperparathyroidism. METHODS: We reviewed records for 401 consecutive patients who underwent parathyroidectomy from 1999 to 2004. Gender, age, preoperative imaging, surgical findings, gland weight and volume, and 6-month calcium levels (Ca) were examined. RESULTS: We identified 289 women and 112 men, 297 of whom had a preoperative sestamibi scan localized to a single gland (localized group; LG). Ninety-six percent of the LG were found to have single-gland disease, and 4% had multigland disease (MGD). In the nonlocalized group (NLG), 76% had single-gland disease and 24% MGD. Mean gland weight was greater in the LG than in the NLG (1128 mg vs 699 mg; P < .05). Mean gland volume was larger in the LG (1.34 cc vs 0.89 cc; P < .05). A localizing sestamibi scan had a positive predictive value (PPV) of 96% and a likelihood ratio of 2.29 for predicting "curative" intraoperative parathyroid hormone drop after removal of a single abnormal gland. Patients were stratified into normocalcemic (NCa) and hypercalcemic (HCa) groups based on 6-month postoperative serum calcium data (n = 328). HCa incidence at 6 months did not differ significantly between the LG (5%) and NLG (3%). A localizing scan had a PPV of 95% for normocalcemia at 6 months. A nonlocalizing scan had a PPV of 21% for HCa at 6 months. CONCLUSIONS: Nonlocalizing sestamibi scans were more common in primary hyperparathyroidism with MGD and were associated with smaller-volume abnormal glands found at operation. Preoperative sestamibi scan-results did not predict HCa at 6 months.

Coexistence of sporadic multiple endocrine neoplasia and scapular ectopic breast. Coincidence or biologically associated?

We describe a patient who presented with sporadic pheochromocytoma and parathyroid adenoma in the absence of medullary thyroid carcinoma, which coexisted with fully developed scapular ectopic breast tissue. If not coincidental, this association might support the concept that all components of multiple endocrine neoplasia type IIA originate from embryonic ectodermal tissue, and that sporadic multiple endocrine neoplasia type IIA, as well as ectopic breast tissue, may result from a noxious event at a critical embryonic stage.

Benign and malignant tumors in patients with acromegaly.

Growth hormone and its principal mediator insulinlike growth factor I are known promoters of normal growth. To determine whether excessive secretion of growth hormone is associated with an increased occurrence of benign and of malignant tumors, we studied records of 87 patients with acromegaly seen in the Lahey Clinic Medical Center (Burlington, Mass) from 1957 to 1988 and compared the rate of tumor occurrence with a control group of patients with pituitary tumors (198) and with findings from a cancer registry. Patients with acromegaly had a 2.45-fold increased rate of malignant tumors (95% confidence interval, 0.98 to 5.04) compared with findings from the tumor registry. Female patients had a higher rate than male patients. The rate of carcinoma of the thyroid was excessive and previously underscribed, but the rate of carcinoma of the colon was not increased as reported by others. Among benign lesions, goiters, predominantly nodular, were seen in 25% of patients in addition to a large number of mesenchymal lesions.

Neuroendocrine tumours.

Neuroendocrine tumours are a heterogeneous group including, for example, carcinoid, gastroenteropancreatic neuroendocrine tumours, pituitary tumours, medullary carcinoma of the thyroid and phaeochromocytomas. They have attracted much attention in recent years, both because they are relatively easy to palliate and because they have indicated the chronic effect of the particular hormone elevated. As neuroendocrine phenotypes became better understood, the definition of neuroendocrine cells changed and is now accepted as referring to cells with neurotransmitter, neuromodulator or neuropeptide hormone production, dense-core secretory granules, and the absence of axons and synapses. Neuroendocrine markers, particularly chromogranin A, are invaluable diagnostically. Study of several neuroendocrine tumours has revealed a genetic etiology, and techniques such as genetic screening have allowed risk stratification and prevention of morbidity in patients carrying the particular mutation. Pharmacological therapy for these often slow-growing tumours, e.g. with somatostatin analogues, has dramatically improved symptom control, and radiolabelled somatostatin analogues offer targeted therapy for metastatic or inoperable disease. In this review, the diagnosis and management of patients with carcinoid, gut neuroendocrine tumours, multiple endocrine neoplasia types 1 and 2, and isolated phaeochromocytoma are evaluated.

Multiple endocrine neoplasia syndromes.

The multiple endocrine neoplasia (MEN) syndromes are characterized by autosomal dominant inheritance with a high degree of penetrance but varying expression. This review gives a classification of these syndromes and a short summary of the historical background. The pathogenesis of the disease and its possible origin in the APUD cell system are discussed together with the mechanisms underlying normal and ectopic hormone production by MEN tumors on the basis of recent findings in molecular endocrinology. The natural history and the clinical manifestations of the different syndromes are described. The sensitivity and discriminative capacity of the tests used to detect the syndromes in an early stage are compared. The choice of therapy and criteria for the timing and extensiveness of treatment are also considered. Lastly, problems associated with the ethical and legal aspects of screening, central registration, and monitoring of relatives at risk are described.

Hypercalcemia in the multiple endocrine neoplasia syndromes.

Multiple endocrine neoplasia includes disorders with hyperfunction of two or more endocrine tissues. In MEN type 1, hyperfunction of the parathyroid glands causing hypercalcemia is the most common clinical presentation. In vitro, suppression of parathyroid tissue by calcium is similar, but the set-point of hyperplastic tissue is shifted as compared with normal. The gene for MEN-1 has been localized to chromosome 11 and is linked to the basic fibroblast growth factor gene. Parathyroidectomy results in a high failure rate with recurrent hyperparathyroidism or autonomous graft function in autotransplanted tissue. Family screening is recommended once every 5 years in first-degree relatives. The approach to hyperparathyroidism in MEN-2 (2A) must be individualized during surgery for medullary thyroid carcinoma. Hyperparathyroidism in MEN-3 (2B) is often associated with normal serum calcium and may not require intervention.

[Disease picture and operative therapy in multiple endocrine adenomatoses (MEA sydrome)]. / Krankheitsbilder und operative Therapie bei multiplen endokrinen Adenomatosen (MEA-Syndrome).

We have outlined the symptoms, diagnostic procedures and operative treatment of "multiple endocrine adenomatosis" (MEA I, IIa und IIb). The priority of the operative procedure whenever two or more clinical syndromes in a patient with MEA are present and the possibility of multiple tumors has to be considered carefully. When there is a tumor of an endocrine organ, it should always bethought about the MEA-syndrome. We report about 9 patients seen in our hospital.

[The molecular genetics of multiple endocrine neoplasia type 2A and 2B].

Multiple endocrine neoplasia (MEN) type 2A (MEN 2A) and type 2B (MEN 2B) are dominantly inherited with a predisposition to endocrine tumors. The responsible genes for MEN 2A and 2B have recently been localized to chromosome 10q 11.2 by genetic and physical mapping. The DNA segment encompasses the RET proto-oncogene. This is a receptor tyrosine kinase gene, which is expressed in medullary thyroid carcinoma and pheochromocytoma. Point mutations in the cysteine-rich domain of the RET were demonstrated in patients with MEN 2A. The cosegregation of these mutations and disease in MEN 2A families indicates that they possess a predisposition endocrine organs to develop into tumors. Biological assessment of the mutant forms in cell culture and transgenic mouse lines should provide further insight as to the role of the RET in the tumor development.

Multiplicity of hormone-secreting tumors: common themes about cause, expression, and management.

CONTEXT: Multiplicity of hormone-secreting tumors occurs in a substantial portion of hormone-excess states. Multiplicity increases the difficulty of management and drives the selection of special strategies. EVIDENCE ACQUISITION: This is a synthesis from publications about tumor development and expression, and also about types of clinical strategy for hormone-secreting tumors. EVIDENCE SYNTHESIS: Comparisons were made between patient groups with solitary tumors vs those with multiple tumors. Major themes with clinical relevance emerged. Usually, tumor multiplicity develops from a genetic susceptibility in all cells of a tissue. This applies to hormone-secreting tumors that begin as either polyclonal (such as in the parathyroids of familial hypocalciuric hypercalcemia) or monoclonal tumors (such as in the parathyroids of multiple endocrine neoplasia type 1 [MEN1]). High penetrance of a hereditary tumor frequently results in bilaterality and in several other types of multiplicity. Managements are better for the hormone excess than for the associated cancers. Management strategies can be categorized broadly as ablation that is total, subtotal, or zero. Examples are discussed for each category, and 1 example of each category is named here: 1) total ablation of the entire tissue with effort to replace ablated functions (for example, in C-cell neoplasia of multiple endocrine neoplasia type 2); 2) subtotal ablation with increased likelihood of persistent disease or recurrent disease (for example, in the parathyroid tumors of MEN1); or 3) no ablation of tissue with or without the use of pharmacotherapy (for example, with blockers for secretion of stomach acid in gastrinomas of MEN1). CONCLUSIONS: Tumor multiplicity usually arises from defects in all cells of the precursor tissue. Even the optimized managements involve compromises. Still, an understanding of pathophysiology and of therapeutic options should guide optimized management.