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T C Friedman

Publications and source records attributed to T C Friedman.

At least 55 records · Page 3Linked to original sources
PubMed1995

Pyroglutamyl peptidase-II ("thyroliberinase") activity in human serum: influence of weight and thyroid status.

The tripeptide hormone, TRH, is metabolized by three enzymes, the most specific of which is pyroglutamyl peptide hydrolase-II (also termed thyroliberinase), a metalloenzyme present in serum and brain. Because pyroglutamyl peptidase-II activity in rat serum is regulated by thyroid hormone levels, we tested the hypothesis that this activity is similarly altered in humans. We studied serum pyroglutamyl peptidase-II activity in 6 patients with hyperthyroidism, 18 patients with hypothyroidism, and 31 euthyroid, normal weight volunteers. Because TRH [or its metabolite cyclo(His-Pro)] is believed to be an important hormone regulating appetite and metabolism, we also evaluated pyroglutamyl peptidase-II activity in 27 euthyroid patients with obesity. Serum pyroglutamyl peptidase-II activity was elevated in patients with hypothyroidism (mean +/- SEM, 33.9 +/- 3.7 nmol/mL.h) compared to that in euthyroid, normal weight volunteers (24.5 +/- 2.8 nmol/mL.h; P < 0.05), but not that in patients with hyperthyroidism (28.3 +/- 4.1 nmol/mL.h; P = NS). Euthyroid obese patients had the highest pyroglutamyl peptidase-II activity (43.6 +/- 2.8 nmol/mL.h; P < 0.0001 vs. normal weight volunteers). Pyroglutamyl peptidase-II activity was positively correlated with body mass index (r2 = 0.30; P < 0.0001). After correction for body mass index, there were no difference in pyroglutamyl peptidase-II activity in hypothyroid, hyperthyroid, and euthyroid individuals. We conclude that serum pyroglutamyl peptidase-II activity is regulated by, or regulates, body weight.

Adult↗
PubMed1994

Corticotropin-releasing hormone production by a small cell carcinoma in a patient with ACTH-dependent Cushing's syndrome.

We describe a patient with Cushing's syndrome and metastatic small cell lung cancer. The plasma ACTH concentrations were markedly elevated (91.6 pmol/L), and the AM cortisol did not suppress by > 50% overnight after administration of 8 mg dexamethasone, both consistent with the ectopic ACTH syndrome. Immunohistochemical studies of a single metastatic tumor specimen, however, demonstrated an absence of ACTH and yet an abundance of corticotropin-releasing hormone (CRH). In addition, radioimmunoassay of the patient's plasma demonstrated persistently elevated CRH concentrations. The majority of the plasma CRH immunoreactivity exhibited the same chromatographic mobility as synthetic r/h CRH (1-41) on HPLC. Failure to evaluate the tumor tissue for the presence of ACTH and/or CRH would have led to the erroneous conclusion that this patient's Cushing's syndrome resulted from paraneoplastic ACTH production. We conclude that immunoassay of plasma for both ACTH and CRH and, perhaps, immunostaining of tumor samples are required to distinguish between the ectopic ACTH and CRH syndromes.

Adrenocorticotropic Hormone↗
PubMed1994

Decreased delta-sleep and plasma delta-sleep-inducing peptide in patients with Cushing syndrome.

To evaluate the sleep disturbances of patients with Cushing syndrome and to examine the relationship between the sleep disturbances and plasma levels of delta-sleep-inducing peptide-like immunoreactivity (DSIP-LI), we performed three polysomnographic/endocrinological studies in patients with Cushing syndrome. In study 1, polysomnography was studied in 12 patients and 12 matched normal volunteers. In addition, DSIP-LI was measured every 30 min for 24 h in 9 patients with Cushing syndrome and 12 normal volunteers. The percentage of time spent in delta sleep (stages 3 and 4) was significantly reduced in patients with Cushing syndrome (5.8 +/- 1.4%; mean +/- SEM) compared to normal volunteers (14.0 +/- 2.5%) (p < 0.01). REM sleep indices, however, were not significantly different between the two groups. There was a significant negative correlation between amount of delta sleep and 08.00 h DSIP-LI (r = -0.43, p < 0.05), which is against the notion of a causal relationship between DSIP-LI and delta sleep. The circadian rhythm of plasma DSIP-LI was found to be similar in Cushing patients and normal volunteers. In study 2, we measured plasma levels of delta-sleep-inducing peptide-like immunoreactivity (DSIP-LI) at 08.00 h in 65 patients with Cushing syndrome and 49 normal volunteers. The 08.00 h DSIP-LI concentrations of 797 +/- 57 pmol/l (mean +/- SEM) in the patients with Cushing syndrome were significantly reduced compared to the level of 1,062 +/- 99 pmol/l found in the normal volunteers (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1994

In vitro processing of proopiomelanocortin by recombinant PC1 (SPC3).

The prohormone convertases, PC1 (SPC3) and PC2, are subtilisin-like serine proteases capable of processing neuropeptide precursors. In cotransfection experiments, other investigators have found that PC1 and PC2 can process POMC to appropriate peptide products. In this study, recombinant rat PC1 was stably expressed in a mouse L-cell line and partially purified. Mouse POMC was cleaved by recombinant PC1 to generate ACTH intermediates, ACTH, ACTH linked to joining peptide, joining peptide, 16-kilodalton N-POMC, N-POMC-(1-74), and beta-lipotropin. Recombinant PC1 was also found to cleave ACTH to ACTH-(1-15) and bovine N-POMC-(1-77) to gamma 3 MSH. The pH optimum of the cleavages was 6.0. We conclude that recombinant PC1 is capable of processing POMC in vitro at all of the paired basic residues, with the exception of Lys-Arg and Lys-Lys in beta-lipotropin and beta-endorphin, respectively. This in vitro study showed a more general specificity of recombinant PC1 for paired and tetrabasic residues of POMC than was previously found in cotransfection experiments. Other cellular regulatory mechanisms probably play a role in limiting the processing of POMC in vivo in the anterior pituitary, where gamma 3 MSH and alpha MSH are not found in significant amounts.

Adrenocorticotropic Hormone↗
PubMed1994

Diurnal rhythm of plasma delta-sleep-inducing peptide in humans: evidence for positive correlation with body temperature and negative correlation with rapid eye movement and slow wave sleep.

Since delta-sleep-inducing peptide (DSIP) was isolated in 1977, numerous reports have suggested that this nonapeptide stimulates delta-sleep [slow wave sleep (SWS)]. Although DSIP-like immunoreactivity (DSIP-LI) has been found in the serum of many animals and man, its diurnal rhythm and relation to sleep stages have not been well defined. We hypothesized that circulating levels of this putative sleep hormone would be highest at night and would probably be elevated before or during episodes of SWS. We, therefore, measured plasma DSIP-LI levels every 30 min for 24 h in 12 normal volunteers in whom we obtained simultaneous polygraphic recordings. We found a distinct diurnal rhythm for plasma DSIP-LI levels, with the maximum at 1500 h and the minimum at 0100 h. DSIP-LI levels were substantially lower in rapid eye movement sleep (P < 0.005) and somewhat lower in SWS (P < 0.05) compared to awake values. DSIP-LI levels did not rise before, during, or after a significant percentage of episodes of SWS. We found, however, that the diurnal rhythm of DSIP-LI closely followed that of body temperature with a high degree of correlation (r2 = 0.66; P < 0.0001). We conclude that endogenous elevations of circulating DSIP may be associated with suppression of slow wave and rapid eye movement sleep, and that the circadian rhythm of this peptide is coupled directly or indirectly to that of body temperature.

Adrenocorticotropic Hormone↗
PubMed1994

Presence of immunoreactive corticotropin-releasing hormone in normal and polycystic human ovaries.

Recently, we demonstrated the presence of immunoreactive (Ir) CRH and its receptors in the rat ovary. To determine whether CRH is also present in human ovaries, we examined ovaries from normal women and patients with the polycystic ovarian syndrome (PCOS). Immunoreactive CRH in normal human ovaries had a similar distribution to that of rat ovarian IrCRH, as determined by immunohistochemistry. Thus, immunoreactivity was intense in the cytoplasm of thecal cells surrounding the ovarian follicles, in luteinized cells of the stroma, and in a subpopulation of cells within the corpora lutea. No IrCRH was present in oocytes of primordial follicles. Polycystic ovaries also had IrCRH in thecal cells; however, CRH immunostaining was less prominent or completely absent from the stroma or the sparsely present corpora lutea and was clearly detected in oocytes of primordial follicles. Using a specific RIA, the IrCRH content in extracts of normal ovaries was higher than that in polycystic ovaries (mean +/- SD, 0.075 +/- 0.02 vs. 0.038 +/- 0.009 pmol/g wet tissue, respectively; P < 0.05). Human follicular fluid samples collected from women undergoing ovarian hyperstimulation for assisted reproduction had low, but detectable, levels of IrCRH (mean +/- SD, 4.975 +/- 1.179 pmol/L), whereas IrCRH was undetectable in concurrently drawn plasma samples. IrCRH detected in normal and polycystic ovaries and in follicular fluid had similar chromatographic mobility to that of rat/human CRH-(1-41) by reverse phase HPLC. We conclude that IrCRH is present in normal human ovaries and follicular fluid, suggesting that this neuropeptide may play a regulatory role in one or more of the various functions of this gonad, such as ovulation and/or luteolysis, through its proinflammatory properties and/or its auto/paracrine regulation of steroid biosynthesis, in analogy to its action on testosterone secretion by the Leydig cell. Its decreased concentration and localization in primary oocytes of polycystic ovaries may be related to the increased androgen biosynthesis by the theca and stroma and/or to the oocyte dysfunction observed in women with the polycystic ovarian syndrome, respectively.

Adolescent↗
PubMed1994

Presence of immunoreactive corticotropin releasing hormone in thyroid lesions.

Corticotropin-releasing hormone (CRH) functions as a regulator of the hypothalamic-pituitary-adrenal axis and coordinator of the stress response. Immunoreactive CRH (IrCRH) is also produced in a variety of inflammatory sites, where this peptide acts as a proinflammatory cytokine. To detect CRH in autoimmune thyroid disease as well as in disorders that may be associated with an inflammatory reaction within this gland, we examined immunohistochemically 45 thyroid lesions, including 12 nodular goiters, 9 cases of Hashimoto thyroiditis, 6 follicular adenomas, 4 follicular and 8 papillary carcinomas, 4 Hürthle cell tumors, 1 medullary cancer, and 1 insular thyroid carcinoma. We also examined the presence of IrCRH in the adjacent normal thyroid parenchyma. The avidin-biotin complex method was employed on formalin-fixed, paraffin-embedded tissue, using a highly specific, affinity-purified polyclonal rabbit anti-CRH antibody. Granular cytoplasmic immunostaining of follicular cells was observed in 100% of the cases of Hashimoto thyroiditis, 77% of the neoplasms and 42% of goiters. The intensity of the staining was more pronounced in Hashimoto thyroiditis and Hürthle cell tumors, whereas the remaining lesions exhibited a heterogeneous staining pattern. No IrCRH was observed in the normal thyroid parenchyma. Using a specific radioimmunoassay, the IrCRH in extracts of simple thyroid goiters, papillary carcinomas, and Hürthle cell tumors ranged between 0.031 and 0.224 pmol/g of wet tissue but was undetectable in normal thyroid parenchyma. The IrCRH molecule in the thyroid gland eluted at the same fraction as synthetic rat/human CRH 1-41 in reverse phase high pressure liquid chromatography. We conclude that IrCRH is present in thyroid lesions, predominantly in those related to autoimmune phenomena, suggesting that this neuropeptide may be directly and/or indirectly involved with inflammatory processes taking place in this gland.

Animals↗
PubMed1993

Corticotropin-releasing hormone in synovial fluids and tissues of patients with rheumatoid arthritis and osteoarthritis.

Inflammation normally results in enhanced synthesis and secretion of hypothalamic corticotropin-releasing hormone (CRH) which, in turn, exerts antiinflammatory effects by virtue of increased adrenal glucocorticoid production. CRH and CRH binding sites are also expressed in the peripheral nervous and immune systems. Our groups have recently shown that CRH is secreted locally in acute carrageenin-induced inflammation in rats and has predominantly proinflammatory effects. We have also shown that CRH is expressed in the joints of Lewis rats with experimental arthritis. To determine if CRH is present in human inflammatory arthritis, we examined synovial fluids and tissues from patients with rheumatoid arthritis (RA) or osteoarthritis (OA) and normal individuals. We found markedly enhanced expression of immunoreactive CRH in situ in synovium from patients, which was significantly greater in RA than in OA (p < 0.01). CRH concentrations were also significantly higher in RA (140 +/- 33 pg/ml, mean +/- SEM; n = 10) than OA (25 +/- 4 pg/ml; n = 6) synovial fluids (p < 0.005). HPLC showed immunoreactive CRH extracted from RA and OA synovial tissues and fluids coeluted with CRH 1-41. CRH mRNA was present in low levels in synovial tissue from patients with RA and, to a lesser extent, OA. In summary, immunoreactive CRH is locally secreted in the synovium of patients with RA and, at lower levels, OA. These data support the view that CRH functions as an autocrine and/or paracrine mediator of inflammation in humans.

Arthritis, Rheumatoid↗
PubMed1993

Purification and characterization of a paired basic residue-specific yeast aspartic protease encoded by the YAP3 gene. Similarity to the mammalian pro-opiomelanocortin-converting enzyme.

Yeast cells express an alternate enzyme encoded by the YAP3 gene which can process pro-alpha-mating factor when this pheromone is overexpressed in KEX2-deficient mutants. The YAP3 gene product is an aspartic protease (YAP3) that cleaves at paired basic residues (Egel-Mittani, M., Flygenring, H.P., and Hansen, M. T. (1990) Yeast 6, 127-137). In this study, the YAP3 gene was overexpressed in the BJ 3501 strain of Saccharomyces cerevisiae. YAP3 was purified to apparent homogeneity using concanavalin A and pepstatin A affinity chromatography. The enzyme was characterized as an M(r) 68,000 glycoprotein with a pH optimum of 4.0-4.5. It was inhibited by pepstatin A and activated by 5 mM Ca2+. YAP3 cleaved at paired basic residues of mouse pro-opiomelanocortin (POMC) to yield adrenocorticotropin (ACTH) and beta-lipotropin (LPH); human beta-LPH to yield beta-endorphin-(1-31), beta-endorphin-(1-29), beta-endorphin-(1-28), gamma-LPH, and beta-melanocyte-stimulating hormone; and bovine N-POMC1-77 to yield gamma 3-melanocyte-stimulating hormone. It also cleaved the tetrabasic residues of ACTH1-39 to yield primarily ACTH1-15 and Lys-Arg-corticotropin-like intermediate lobe peptide. The physical properties, pH optimum, and specificity of YAP3 indicate that it is a homologue of the mammalian POMC-converting enzyme (EC 3.4.23.17), a paired basic residue-specific aspartic protease from bovine pituitary intermediate lobe secretory granules (Loh, Y. P., Parish, D.C., and Tuteja, R. (1985) J. Biol. Chem. 260, 7194-7205).

Adrenocorticotropic Hormone↗
PubMed1993

Immunoreactive corticotropin-releasing hormone and its binding sites in the rat ovary.

Corticotropin-releasing hormone (CRH), the principal neuropeptide regulator of pituitary ACTH secretion, is also produced at peripheral inflammatory sites, where it acts as a proinflammatory cytokine, and by the Leydig cell of the testis, where it exerts autocrine inhibition of testosterone biosynthesis. Because key ovarian functions, such as ovulation and luteolysis, represent aseptic inflammatory responses, and because the theca cell is the functional equivalent of the Leydig cell, we explored the CRH presence in the ovary, first, by specific CRH immunohistochemistry of adult cycling female Sprague-Dawley rat ovaries. We detected cytoplasmic immunoreactive CRH (IrCRH) in theca and stromal cells and in cells within the corpora lutea, at all phases of the estrous cycle. Using a specific radioimmunoassay, we measured IrCRH in extracts of rat ovaries (0.042-0.126 pmol/g wet tissue). The mobility of the ovarian IrCRH molecule was similar to that of rat/human CRH by reverse phase HPLC. To investigate the CRH action in the ovary, we identified, characterized, and localized CRH receptors in the rat ovary. Binding was linear with increasing tissue concentration, saturable, and of high affinity. Scatchard analysis of 125I-Tyr-ovine CRH competitive displacement curves indicated a high affinity binding site with a Kd of approximately 6 nM and a Bmax value of approximately 61 fM/mg protein. Autoradiographic studies revealed CRH receptors primarily in ovarian theca and stroma. We conclude that IrCRH and CRH receptors are present in rat ovaries, suggesting that this neuropeptide may play a regulatory role in this gonad, perhaps through its proinflammatory properties and/or by participating in the auto/paracrine regulation of steroid biosynthesis. Functional studies are necessary to define the role(s) of CRH in the ovary.

Animals↗
PubMed1993

Generation of 1-37 and 1-38 forms of adrenocorticotropin by mono- and dipeptidyl serine carboxypeptidase activities in bovine pituitary secretory vesicles.

ACTH is a 39-amino acid peptide synthesized in the pituitary as part of the precursor molecule, POMC. Analysis of bovine anterior pituitary homogenates and secretory vesicles revealed that in addition to ACTH-(1-39), ACTH-(1-37) and ACTH-(1-38) were also present in the lobe, indicating that carboxyl-terminal processing of ACTH-(1-39) occurred in vivo. Mono- and dipe;tidyl carboxypeptidase activities that cleaved ACTH-(1-39) were detected in bovine intermediate and anterior pituitary secretory vesicle membranes and characterized. The dipeptidyl carboxypeptidase activity liberated ACTH-(1-37) and the dipeptide, Glu-Phe, and the monocarboxypeptidase activity generated, to a smaller extent, ACTH-(1-38) and phenylalanine from ACTH-(1-39). Kinetic studies indicated that the formation of ACTH-(1-37) occurred within minutes, whereas the formation of ACTH-(1-38) occurred within hours. Both enzymatic activities had a pH optimum of 5.5 and a Km of 14-18 microM for ACTH-(1-39), and were inhibited by serine and some thiol, but not metallo- or aspartic protease inhibitors. These unique serine carboxypeptidase(s) may function as a converting enzyme in vivo.

Adrenocorticotropic Hormone↗
PubMed1993

Thyrotropin-secreting pituitary carcinoma.

Pituitary tumors rarely metastasize outside the central nervous system. Of the more than 100 reported TSH-secreting adenomas, we now describe the first carcinoma. A 40-yr-old woman had transsphenoidal surgery for a large TSH-secreting pituitary adenoma in 1984. She had increased thyroid hormone levels with a TSH that varied from 16-31 microU/mL, and an unusually high alpha-subunit that ranged from 125-150 ng/mL. Because of residual tumor, she had a left craniotomy in 1985 followed by radiation. Despite these therapies, she had a residual tumor that remained stable until January 1989 when her tumor nearly doubled in size. She received radiation therapy and octreotide with marked diminution of the tumor and clinical improvement. In August 1989, she presented with leg weakness, and magnetic resonance imaging revealed a large sacral mass. A biopsy confirmed that the sacral mass was a metastasis from the pituitary tumor. Due to additional metastases in the lung, she received 5-fluorouracil, cytoxan, and adriamycin, with marked decrease in her lesions. Further substantiation of the metastatic pituitary tumor was made when the patient returned in December 1989 with a pleural effusion containing pituitary tumor cells. Of all the reported cases of TSH-secreting adenomas, this case had the highest alpha-subunit portending future metastases. Furthermore, the apparent response to octreotide and response to chemotherapy are encouraging and suggest that new therapies should be explored. Finally, since TSH-secreting adenomas tend to be more invasive than other pituitary tumors, this case underscores the need for early diagnosis and aggressive treatment of these tumors.

Adult↗
PubMed1993

Posterior subcapsular cataract in endogenous Cushing syndrome: an uncommon manifestation.

PURPOSE: Posterior subcapsular cataract is a well-known complication of longstanding glucocorticoid therapy (exogenous Cushing syndrome). The purpose of this study was to examine the effect of chronic endogenous hypercortisolism (endogenous Cushing syndrome) on the human lens. METHODS: Sixty consecutive patients (8 to 67 years of age, 46 females, 14 males) with endogenous Cushing syndrome were studied. The exposure to cortisol was estimated based on the duration of the disease and measurements of the 24-hour urine free cortisol excretion. Complete ocular examination included biomicroscopy of the lens after dilation. RESULTS: Duration from the onset of endogenous Cushing syndrome ranged from 1 to 20 years (mean +/- SD, 5.5 +/- 3.7). Urine free cortisol excretion ranged from 250 to 3065 micrograms/24 hr (mean +/- SD, 693 +/- 547; normal values, 20 to 90 micrograms/24 hr). Only two of the 60 patients (3.3%) had posterior subcapsular cataract. This low prevalence contrasts to the high prevalence attributed to glucocorticoid therapy with grossly equivalent total dosage of glucocorticoids. CONCLUSION: It was concluded that posterior subcapsular cataract is an infrequent complication of endogenous hypercortisolism compared to exogenous Cushing syndrome. Because the total exposure to endogenous glucocorticoids was not lower than that of exogenous glucocorticoid therapy, a potential explanation for this difference might be the exposure of the lens to the natural (cortisol) rather than a synthetic glucocorticoid or pharmacokinetic differences of glucocorticoids between the two forms of Cushing syndrome.

Adolescent↗
PubMed1992

Familial syndrome of endocrine and neuroectodermal abnormalities.

We report on a previously undescribed combination of endocrine and neuroectodermal abnormalities in four sibs from Burma. These abnormalities include low growth hormone levels in response to provocative stimuli, delayed puberty associated with prepubertal levels of gonadotropins in the males and pubertal levels of gonadotropins in the females, type II diabetes mellitus with elevated insulin levels, mild mental retardation, sensori-neural deafness, and alopecia without pili torti. They also had a characteristic facial appearance and fleshy hands and feet. This family appears to have a previously undescribed combination of endocrine and neuroectodermal abnormalities.

Adolescent↗
PubMed1992

Processing of adrenocorticotropin by two proteases in bovine intermediate lobe secretory vesicle membranes. A distinct acidic, tetrabasic residue-specific calcium-activated serine protease and a PC2-like enzyme.

Adrenocorticotropin (ACTH) is cleaved at the tetrabasic residue site, in pituitary intermediate lobe secretory vesicles, to yield ACTH1-17 and corticotropin-like intermediate lobe peptide (CLIP). ACTH1-17 is then converted to alpha-melanocyte-stimulating hormone (N-AcACTH1-13NH2) by first removing the Lys15-Lys16-Arg17 residues, followed by amidation of the COOH terminus and acetylation of the NH2 terminus. Bovine intermediate lobe secretory vesicle membranes were screened for proteolytic enzyme activity that will cleave the tetrabasic residues of ACTH. Two activities with pH optima of 5.0-6.0 and 7.5-8.0 were detected. The acidic, ACTH-converting enzyme cleaved ACTH1-39 at the tetrabasic residues between the Arg17-Arg18 bond to yield ACTH1-17 and CLIP, but did not cleave paired basic residues of pro-opiomelanocortin. This enzyme activity was characterized as a Ca(2+)-activated serine protease with unique specificity for the tetrabasic residues of ACTH1-39. The neutral activity preferentially generated ACTH1-17 and to a small extent ACTH1-16 from ACTH1-39 and ACTH1-24. This enzyme activity was Ca(2+)-dependent but was not inhibited by serine or aspartic protease inhibitors. The neutral activity was significantly immunodepleted by antiserum raised against bovine PC2/PC3, and together with specificity studies, suggests that the enzyme is a PC2-like serine protease. The pH optimum, distinct specificity for tetrabasic residues, and subcellular localization of the acidic ACTH-converting enzyme indicate a function of this enzyme in the in vivo conversion of ACTH1-39 to alpha-melanocyte-stimulating hormone in intermediate lobe secretory vesicles which have an acidic internal pH.

Adrenocorticotropic Hormone↗
PubMed1992

Distinction between hyperaldosteronism due to bilateral hyperplasia and unilateral aldosteronoma: reliability of CT.

Hyperaldosteronism due to a unilateral adenoma must be distinguished from hyperaldosteronism due to bilateral hyperplasia to enable the proper choice between surgical treatment (for adenoma) or medical treatment (for hyperplasia). To compare the efficacy of computed tomography (CT) and adrenal venous sampling, both examinations were performed in 24 patients with primary aldosteronism. All patients with a diagnosis of adenoma based on findings at venous sampling underwent adrenalectomy. The CT-based diagnosis was unilateral aldosteronoma in 17 patients and hyperplasia in seven patients. On the basis of venous sampling, unilateral adenoma was diagnosed in 22 patients; this diagnosis was confirmed by means of unilateral adrenalectomy in 21 patients. The most common error was diagnosis of hyperplasia based on the presence of bilateral nodules on CT scans: In six of seven patients with such a diagnosis, venous sampling and subsequent surgery revealed a unilateral adenoma. In hyperaldosteronism with multiple bilateral nodules, CT cannot reliably permit distinction between hyperplasia and adenoma.

Adenoma↗
PubMed1991

Frequent occurrence of asplenism and cholelithiasis in patients with autoimmune polyglandular disease type I.

PURPOSE: This study assesses the occurrence of asplenism and gallstones in patients with autoimmune polyglandular disease type I (APG I). PATIENTS AND METHODS: Nine patients with APG I (ages 14 to 48) were studied at the National Institutes of Health. Each patient received endocrine testing, a careful examination of his or her peripheral blood smear, lymphocyte immunophenotyping, a liver-spleen scan, and either an upper abdominal ultrasound or a computer-assisted tomogram to evaluate the spleen and gallbladder. RESULTS: We documented asplenism in four patients and cholelithiasis in four patients, with two patients having both conditions. The patients with asplenism had Howell-Jolly bodies on peripheral blood smears, lack of splenic uptake by liver-spleen scan, and absent spleens by abdominal computed tomographic scan or ultrasound evaluation. The clinical presentation of the patients with cholelithiasis ranged from acute symptoms requiring surgery to asymptomatic gallstones. Lymphocyte immunophenotyping did not reveal consistent changes in either B- or T-cell subpopulations in the patients studied. CONCLUSION: Asplenism and gallstones occur frequently in patients with APG I. In addition to careful examination of the peripheral blood smear for Howell-Jolly bodies to screen for asplenism, we recommend an abdominal ultrasound to detect asplenism and/or gallstones in all patients with APG I. Appropriate immunizations and antibiotic coverage may be helpful in those patients with absent spleens.

Adolescent↗