Admissions of injection drug users to drug abuse treatment following HIV counseling and testing.

The outcomes of counseling and testing programs related to human immunodeficiency virus (HIV) infection and risk of infection among injection drug users (IDUs) are not well known or understood. A counseling and testing outcome of potential public health importance is attaining admission to drug abuse treatment by those IDUs who are either infected or who are at high risk of becoming infected. The authors investigated factors related to admission to drug abuse treatment among 519 IDUs who received HIV counseling and testing from September 1987 through December 1990 at a men's prison and at community-based testing sites in Worcester, MA. By June 1991, 123 of the 519 IDUs (24 percent) had been admitted to treatment. Variables associated with their admission included a long history of drug injection, frequent recent drug injection, cleaning injection equipment using bleach, prior drug treatment, and a positive HIV test result. Logistic regression analyses, controlling for effects of recruitment site, year, sex, and area of residence, generally confirmed the associations. IDUs in the study population who were HIV-infected sought treatment or were admitted to treatment more frequently than those who were not infected. The results indicate that access to drug abuse treatment should be facilitated for high-risk IDUs and for those who have begun to inject drugs recently.

Haemangiopericytoma presenting with intracerebral haemorrhage. Case report and review of literature.

A case of an intracerebral bleeding from haemangiopericytoma is reported. To our knowledge it is the first published case. The literature concerning apoplectic presentation of brain tumours is reviewed.

Age-related probability of development of hereditary medullary thyroid carcinoma.

Hereditary medullary thyroid carcinoma is inherited as an autosomal dominant trait; at birth each child of an affected parent has a 50% chance of developing the disease. Measurement of plasma calcitonin concentrations after provocative calcium or pentagastrin stimulation has proved useful in the early diagnosis of this disease. To determine the age-related risk of conversion from a negative to a positive provocative test, 445 members of 11 kindreds were studied with sequential tests. Of 159 family members with a 50% risk at birth of developing medullary thyroid carcinoma 38 converted from a negative to a positive test result (mean age of conversion was 15 years). By means of methods previously described for determining the age-related probability for developing Huntington chorea, we present a method for determining the probability of development of medullary thyroid carcinoma. An individual at risk whose test result was negative had the following probability of converting to a positive test result at a later date: age (years)/probability, 0/0.5; 5/0.49; 10/0.41; 15/0.25; 20/0.16; 25/0.10, 30/0.05; and 35/0. We conclude that hereditary medullary thyroid carcinoma is regularly detectable in the pediatric age group and that screening should begin by age 5 years and be continued at regular intervals until age 35.

Surgical cure of prolactinoma reverses abnormal prolactin repsonse to carbidopa/L-dopa.

To determine whether the abnormalities in dopaminergic regulation of PRL secretion in patients with prolactinomas persist after resection of the adenoma, we evaluated PRL inhibitory responses to L-dopa alone and L-dopa given after pretreatment with the dopa decarboxylase inhibitor carbidopa before and after transsphenoidal selective resection of prolactinomas in 23 women. Eighteen women were cured by surgery (normal PRL, menses, no galactorrhea), while 5 women were not cured. Preoperatively, the PRL inhibitory responses to L-dopa cured, 4 .3 +/- 3.8%; uncured, 50.1 +/- 5.5% of baseline) was blunted by pretreatment with the decarboxylase inhibitor carbidopa (cured, 79.1 +/- 4.1%; uncured, 76.8 +/- 9.2%). Postoperatively, this blunting disappeared in the cured patients (L-dopa, 49.1 +/- 3.5%; carbidopa/L-dopa, 56.3 +/- 5.1%), but the blunting persisted in the uncured patients (L-dopa, 49.3 +/- 7.9%; carbidopa/L-dopa, 69.3 +/- 4.2%). The return to normal of the carbidopa/L-dopa test in cured prolactinoma patients after surgery is evidence that in these individuals, preoperative abnormalities of secretion are due to either intrinsic abnormalities of the tumor or alteration of hypothalamic function secondary to tumor secretion. In those patients not cured by surgery, dynamic tests of function remain abnormal, findings attributable to either incomplete tumor resection or the presence, in some patients, of underlying hypothalamic dysregulation.

Effects of L-dopa and bromocriptine on calcitonin secretion in medullary thyroid carcinoma.

The secretion of calcitonin (CT) by thyroid C cells has been reported to be reduced by dopamine in vitro and by L-dopa in patients with medullary thyroid carcinoma (MTC). These results have suggested that dopa uptake ad decarboxylation to dopamine may play an inhibitory role in the control of CT secretion. We studied the effects of either L-dopa or bromocriptine, a dopamine agonist, on CT secretion in 11 patients with MTC. Seven patients had multiple endocrine adenomatosis type II (MEA II), 1 had MEA III, and 3 had sporadic MTC. Metastatic disease was confirmed in 8, was probable in 2, and was absent in 1. L-Dopa (500 mg orally) was given to 10 patients in 12 trials. Serum obtained serially for CT measurement RIA over a 4-h period showed a fall in 4 instances in 3 patients; there was no decrease in 7 patients. Absorption of L-dopa was confirmed by the finding of the expected rise in serum GH concentration in all nonresponders except 1. Bromocriptine administered in increasing doses (7.5-50 mg/day) for periods from 4-18 weeks in 5 patients with metastatic disease failed to lower the serum CT concentration in any patient. In 2 of 4 cases, pentagastrin-induced CT release was augmented during bromocriptine administration. These results show L-dopa suppression of CT secretion only in a minority of patients with MTC; the lack of response to bromocriptine suggessts that dopamine receptor stimulation by dopaminergic ergots does not inhibit CT secretion in this same group of patients.

Natural history of familial medullary thyroid carcinoma: effect of a program for early diagnosis.

To detect familial medullary thyroid carcinoma in a premetastatic stage, we administered tests provocative of calcitonin secretion (infusion of calcium or pentagastrin or both) each year for seven years to members of a pedigree now numbering 107. Since 1970, 21 patients converted from normal to abnormal secretory responses (two separate tests in which calcitonin levels exceeded 0.58 ng per milliliter). Twenty of 21 glands removed showed C-cell hyperplasia, and eight of the 20 also showed foci of carcinoma. As compared to the 12 patients with tumors detected during the first year of screening, all of whom had bilateral carcinoma (seven of 12 with local metastases), later carcinomas were smaller (mean diameter of 0.2 vs. 0.8 cm), were unilateral (in all but two cases) and occurred in younger patients (mean age of 14.9 vs. 36.4 years), and none had detectable metastases.

Total thyroidectomy for occult familial medullary carcinoma of the thyroid in children.

Experience with 17 children in one kindred with familial medullary carcinoma of the thyroid and pheochromocytoma has demonstrated the utility and validity of periodic provocative testing by calcium infusion or pentagastrin injection in the identification of children with early medullary carcinoma of the thyroid or its premalignant precursor, C-cell hyperplasia. In these 17 patients with two consecutive elevations of calcitonin levels greater than 0.55 ng/ml after stimulation all but one have had MTC or CCH at operation. Total thyroidectomy has been well tolerated and can be performed with an acceptably low incidence of complications in this group of patients.

Adrenal medullary hyperplasia. A morphometric analysis in patients with familial medullary thyroid carcinoma.

The syndrome of familial medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia is inherited as an autosomal dominant trait, and is characterized by development of bilateral and multicentric thyroidal and adrenal medullary tumors. One of the earliest manifestations of adrenal medullary hyperfunction in patients with this syndrome is an increased ratio of epinephrine to norepinephrine in urine. In order to define the morphologic correlates of these early catecholamine abnormalities in a large kindred with familial MTC, a morphometric analysis based on a point-counting system to asses adrenal medullary volume was undertaken. These studies clearly revealed adrenal medullary hyperplasia as reflected by a two- to three-fold increase in medullary volume and weight as compared to age- and sex-matched controls. The increase in total medullary mass resulted from diffuse and multifocal modular proliferations of adrenal medullary cells primarily within the head and body regions of the glands. These results support the hypothesis that the pheochromocytomas in patients with familial MTC may, in fact, represent extreme degrees of nodular hyperplasia of the medulla.

Natural history of the familial medullary thyroid carcinoma-pheochromocytoma syndrome and the identification of preneoplastic stages by screening studies: a five-year report.

1. In the fifth year of followup, 8 of 12 original patients thyroidectomized for MTC, diagnosed solely by abnormal calcitonin values, are disease free by all criteria. Elevated calcitonin levels are the only manifestation of active disease in three patients with presumed metastases. 2. Routine annual screening of susceptible individuals is a practical measure and has in 6 cases detected the premalignant condition of G-cell hyperplasia and in 1 patient a premetastatic state of MTC. It is premature to conclude that yearly screening is sufficient to detect all cases of premetastatic disease and for this reason we are recommending a yearly screen with pentagastrin and calcium tests and the more convenient pentagastrin test at 6 month intervals for those in the high-risk age group between 8 and 18. If screening at such intervals proves to be ineffective in preventing the disease in every case, consideration must be given to prophylactic thyroidectomy although we are not currently recommending this precedure. 3. Pentagastrin injection is often a more effective secretagogue for calcitonin than is calcium infusion, but this is not uniformly true. We therefore recommend use of both tests as the most appropriate screening procedure. 4. Epinephrine is a major secretory product of pheochromocytomas in the J-kindred and sequential E/N ratios may be of use in the early detection of pheochromocytoma in other kindreds. 5. Adrenal medullary hyperplasia has been found in 3 adrenal glands and is probably a preneoplastic condition analogous to C-cell hyperplasia.