Enzootic simian piroplasm (Entopolypoides macaci ) in wild-caught Kenyan non-human primates.

BACKGROUND: Three species of non-human primates comprising African green monkeys (AGMs), (Cercopithecus aethiops, n = 89), Syke's monkeys (Cercopithecus mitis, n = 60) and olive baboons (Papio cynocephalus anubis, n = 30), were screened for Entopolypoides macaci. METHODS: Observation of blood smears prepared from these animals revealed E. macaci infection rate of 42.7% in AGMs, 35% in Syke's monkeys and 33.3% in baboons. RESULTS: Gender infection rate was 38.2% in females and 29% in males. Statistically, there was no significant difference in infection rates between the monkey species and sexes (P > 0.05). Subsequent indirect immuno fluorescent antibody test supported the morphological appearance of E. macaci observed by microscopy. Sera from infected animals reacted positively (1:625) with E. macaci antigen, but not to Babesia bigemina or B. bovis antigen at 1:125 titer. CONCLUSION: This study has revealed high prevalence of E. macaci infection in all three widely distributed Kenyan non-human primates. With the continued use of these animals as models for human parasitic diseases, the presence of this highly enzootic parasite should be noted.

Pregnancy-associated Cushing's syndrome secondary to a luteinizing hormone/human chorionic gonadotropin receptor-positive adrenal carcinoma.

Cushing's syndrome occurring during pregnancy is frequently due to an adrenal neoplasm. Adrenal gland tumors occasionally respond to luteinizing hormone (LH) or human chorionic gonadotropin (hCG). We report a case of Cushing's syndrome during and following pregnancy due to an adrenal carcinoma which expressed the LH/hCG receptor. The presence of these receptors may have led to the growth and function of the tumor during pregnancy.

Lack of association between hyperprolactinemia and colon carcinoma.

Two recent studies reported that many patients with colorectal carcinoma have elevated serum prolactin (PRL) concentrations and have suggested ectopic PRL secretion as the cause. In the present study, serum PRL was minimally elevated in 16 of 116 colon cancer patients and 2 of 25 control subjects; medications or chemotherapy appeared to be responsible for the PRL elevations in 11 of 16 cancer patients. Serum PRL was not correlated with either plasma carcinoembryonic antigen or disease stage. Preoperative and postoperative serum PRL concentrations were similar in 26 evaluated patients. None of 19 colorectal tumors was positive for PRL staining by immunohistochemistry. Thus, we could not confirm previous reports of frequent hyperprolactinemia in patients with colorectal cancer; factors such as medications, anxiety, pain, and nausea may have raised serum PRL in these earlier studies. Serum PRL is not a useful marker for colon carcinoma, at least in patients in the United States.

Endocrine effects of erythropoietin.

Uremic men may manifest a variety of hormonal abnormalities, including decreased serum concentrations of testosterone and thyroid hormones and increased serum levels of growth hormone and prolactin. Some previous investigations have reported that erythropoietin therapy may reverse these hormonal changes. To investigate this possibility further, we measured serum prolactin, testosterone, LH, FSH, TSH, free thyroxine, triiodothyronine, growth hormone and IGF-I in 21 generally elderly male hemodialysis patients before and during erythropoietin therapy; many of the patients also received an anabolic steroid or metoclopramide treatment. Despite a significant erythropoietic response in a majority of the subjects, no significant changes were seen in any of the hormonal parameters other than a small decrease in serum growth hormone concentrations. Advanced age and chronic illness in our patients may have played a role in limiting the hormonal response reported by others.

Effects of commonly prescribed nonsteroidal anti-inflammatory drugs on thyroid hormone measurements.

PURPOSE: To assess the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on thyroid function tests. PATIENTS AND METHODS: Eighty-nine patients receiving NSAIDs and 22 control subjects not taking NSAIDs were studied in a cross-sectional survey at Veterans Affairs and University hospitals. Measurements of serum thyroxine (T4), free T4 index, triiodothyronine (T3), and thyrotropin (thyroid-stimulating hormone [TSH]) were obtained for all subjects. RESULTS: Serum T4 measurements were lowered only in salsalate-treated patients, while serum T3 was depressed in patients receiving salsalate, diclofenac sodium, and naproxen. Serum T4 and T3 were unchanged in patients treated with diflunisal, ibuprofen, indomethacin, piroxicam, or sulindac. Serum TSH was normal in all subjects. CONCLUSIONS: Several NSAIDs can lower serum thyroid hormone concentrations, principally by interfering with the binding of T4 and T3 to serum carrier proteins; patients taking these drugs remain euthyroid. Awareness of these interactions may prevent unnecessary diagnostic or therapeutic interventions.

Differential tissue regulation of the insulin-like growth factors in rats bearing the MStT/W15 pituitary tumor.

The content of insulin-like growth factors, IGF-I and IGF-II, was measured in tissues of rats bearing a transplantable mammosomatotrophic tumor, MStT/W15. Serum IGF-I was elevated in tumor-implanted rats [2,557 +/- (SE) 419 vs. 891 +/- 100 ng/ml], and tumor tissue concentrations of IGF-I were increased (321 +/- 16 ng/g) in comparison to control liver tissue (160 +/- 5 ng/g) or control pituitary (80 +/- 3 ng/g). The IGF-I levels were significantly increased in most peripheral tissues in the tumor-bearing rats with the exception of the liver. In support of this finding, messenger RNA for prepro IGF-I was likewise not increased in the livers of tumor-bearing rats, nor was there an increase in the growth hormone-dependent IGF-binding protein, BP-3, in the liver or serum of these animals. All tumors had detectable levels of prepro IGF-I mRNA which was, however, less than 50% of that noted in normal control liver. The tumors also expressed an IGF-BP which was identified as IGF-BP-2 by immunoblotting. Serum concentrations of IGF-II were similar in control and tumor-bearing animals (approximately 70 ng/ml). IGF-II levels in the tumor (90 +/- 5 ng/g) were significantly higher than levels in control liver (34 +/- 2 ng/g), but similar to those found in normal pituitary (165 +/- 24 ng/g). In peripheral tissues, IGF-II concentrations were selectively increased in skeletal muscle and heart of tumor-bearing rats. These data demonstrate tissue-specific regulation of IGF-I and IGF-II. Paradoxically, the liver does not appear to be stimulated over control levels by high serum growth hormone levels, since neither IGF-I peptide, IGF-I mRNA, nor IGF-BP-3 levels are increased in livers of tumor-bearing rats. This suggests that the increase in serum IGF-I in these animals is due to increased production of IGF-I by the tumors themselves and by nonhepatic peripheral tissues and further that hepatic responsiveness to growth hormone is diminished in these tumor-bearing animals.

On the nature of serum prolactin in two patients with macroprolactinemia.

OBJECTIVE: To further characterize the high molecular weight (MW) forms of prolactin (PRL) present in patients with macroprolactinemia. DESIGN: Case reports with laboratory investigations. SETTING: Academic medical centers. PATIENTS: Two patients with macroprolactinemia. INTERVENTIONS: Measurements of PRL concentrations before and after chromatographic separations. RESULTS: The majority of serum PRL had an estimated MW of at least 669 kd in the first patient and approximately 171 kd in the second. During a pregnancy, a new form of PRL (MW 291 kd) appeared in the first patient's serum and persisted for at least 3 years. Immunoprecipitation and polyacrylamide gel electrophoresis under reducing and denaturing conditions revealed that the largest form of PRL (MW 669 kd) was composed mostly of 25 kd glycosylated PRL; intermediate forms (171 kd and 291 kd) were composed of roughly equal portions of 25 kd glycosylated PRL and 23 kd nonglycosylated PRL, whereas "little" PRL in these patients was composed primarily of 23 kd nonglycosylated PRL. Injection of the first patient's serum into rats demonstrated that the human PRL (hPRL) immunoreactivity was cleared from the serum more slowly than the PRL from sera containing predominantly little hPRL; after stimulation with thyrotropin-releasing hormone in the second patient, serum PRL concentrations decayed more slowly than observed in normal subjects. CONCLUSIONS: Large forms of serum PRL are at least partially glycosylated. These large forms are heterogeneous, both within and among patients. Delayed clearance may account for increased serum PRL concentrations in patients with macroprolactinemia.

Multiple hamartoma syndrome (Cowden's disease) associated with renal cell carcinoma and primary neuroendocrine carcinoma of the skin (Merkel cell carcinoma).

A case of multiple hamartoma syndrome (Cowden's disease) associated with renal cell adenocarcinoma and primary neuroendocrine carcinoma of the skin is described. Neither of these neoplasms has been documented previously in association with this genodermatosis. A search for epidermal growth factor receptor (c-erb-B protooncogene) gene abnormalities in the kidney, liver, and thyroid, as well as in tissue of the primary neuroendocrine carcinoma, was negative. Serum obtained from the patient before his death contained elevated levels of both chromogranin A (2641 ng/mL; normal level, less than 20 ng/mL) and calcitonin (517 pg/mL; normal level, less than 200 pg/mL), suggesting that the patient's principal tumor was neuroendocrine in origin.

Prolactin responses to phenylalanine and tyrosine in phenylketonuria.

In normal subjects, ingestion of tyrosine or phenylalanine stimulates prolactin (PRL) secretion. In patients with phenylketonuria (PKU), we found normal PRL responses to phenylalanine, demonstrating that conversion of phenylalanine to tyrosine is not necessary for PRL stimulation. PKU patients also showed greater PRL responses to tyrosine during dietary phenylalanine restriction than when consuming an unrestricted diet; this finding is consistent with inhibition by phenylalanine of tyrosine transport across the blood-brain barrier. Such competitive inhibition of a normal brain function may serve as a model for some of the neurotoxic effects of phenylalanine in PKU.

Postmenopausal uterine bleeding due to estrogen production by gonadotropin-secreting lung tumors.

Two postmenopausal women are described who had uterine bleeding due to hormone production by lung tumors--a large cell carcinoma in one case and a choriocarcinoma in the other. Both tumors stained positively for one or more placental peptides (human chorionic gonadotropin [hCG], placental lactogen, or pregnancy-specific beta-1 glycoprotein) and both patients had extremely elevated serum levels of hCG, suggesting the tumors had some placental-like endocrine function. Clinical and hormonal data supported the concept that the uterine bleeding resulted from estrogen excess due to steroid bio-transformation by the tumors.

CSF and endocrine studies of premenstrual syndrome.

Eight women with prospectively documented premenstrual syndrome (PMS) underwent multiple samplings for estradiol, progesterone, prolactin, cortisol, and plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) during an asymptomatic midcycle (late follicular) and a symptomatic premenstrual (late luteal) phase of the menstrual cycle. Cerebrospinal fluid (CSF) was collected for analysis of MHPG, norepinephrine (NE), 5-hydroxyindoleacetic acid (5-HIAA), dihydroxyphenylacetic acid (DOPAC), gamma-aminobutyric acid (GABA), homovanillic acid (HVA), tyrosine, tryptophan, beta-endorphin, prostaglandins, adrenocorticotropic hormone (ACTH), and arginine vasopressin (AVP). In subsequent months, a dexamethasone suppression test (DST) and a thyrotropin-releasing hormone (TRH) stimulation test were performed during midcycle and premenstrual phases. Significant results included increased CSF concentrations of MHPG in the premenstrual, as compared with the midcycle, phase of the cycle, and increased plasma cortisol concentrations during the midcycle phase. The DST showed a 62% overall rate of nonsuppression, irrespective of menstrual cycle phase. Though there were no abnormalities of thyrotropin-stimulating hormone (TSH) after TRH stimulation, the mean delta maximum prolactin values after TRH stimulation were higher than reported normal values both at midcycle and premenstrually. These pilot data suggest hormonal axes that might be worthy of further systematic investigation in future studies of PMS.

Evidence for an intracerebral action of phenylalanine in stimulation of prolactin secretion: interaction of large neutral amino acids.

Phenylalanine stimulates PRL secretion when given orally or iv to normal individuals. To differentiate between hypothalamic and pituitary sites of action, we examined the effects of concurrent infusion of valine on the PRL response to iv phenylalanine in eight normal men. Since large neutral amino acids share the same high affinity blood-brain barrier transport system, entry of phenylalanine into the brain will be diminished by the simultaneous presence of high serum concentrations of valine; the pituitary, lying outside the blood-brain barrier, is not subject to these competitive effects. Valine significantly blunted the PRL response to phenylalanine, supporting an effect of phenylalanine within the blood-brain barrier to stimulate PRL release.

Stimulation of pituitary hormone secretion by neurotransmitter amino acids in humans.

The effects of several neurotransmitter amino acids on pituitary hormone secretion were examined in normal humans. Oral administration of 10 g of glutamic acid stimulated the secretion of prolactin (PRL) and cortisol to approximately twice baseline values, with no effect on GH, TSH or LH. Aspartic acid (10 g), taurine (5 g), and cysteine (5 or 10 g) had no consistent effect on any hormone measured, although the lack of effect of aspartic acid may relate to the modest increments in serum concentration achieved. Glutamic acid may be an important modulator of PRL and ACTH secretion in humans.

Serum prolactin and aging: basal values and changes with estrogen use and hypothyroidism.

We studied basal serum prolactin in older (greater than age 50) men (N = 501) and women (N = 384) using younger adults for comparison and excluding those taking medications. Serum prolactin rose slightly with increasing age in men; it fell slightly in women until age 80, when it rose slightly. Men and women were not different except for the higher value in women at age 20 to 29. Serum prolactin did not fall after the menopause, while estrogen treatment had no effect on older women and caused only a slight rise in older men. Thyroid deficiency had only a minimal effect and did not raise the serum prolactin above 25 ng/ml. The prevalence of clearly elevated values (greater than 20 ng/ml) was only 1.3% in women and 0.6% in men above age 50; there is little evidence for a significant prevalence of prolactin-secreting adenomata in older persons. In older persons, prolactin-secreting tumors are uncommon, and neither thyroid failure nor estrogen therapy are good explanations for a clearly elevated serum prolactin.

Prolactin stimulation by protein is mediated by amino acids in humans.

In normal humans, ingestion of protein stimulates PRL secretion. I investigated the mechanism of this effect by feeding free amino acids, both singly and in combination, to normal subjects. The serum PRL response to a high protein liquid mixed meal was duplicated by ingestion of an equivalent free amino acid mixture, indicating that intact protein or peptides are not required. The time course of the response and the presence of normal responses in two vagotomized subjects suggest that neither traditional gut hormones nor vagus nerve activity is involved in this response. Of the single amino acids tested, phenylalanine and tyrosine were the most potent stimulators of PRL secretion and can account for most, if not all, of the PRL-releasing activity of the mixed meal. D-Phenylalanine, the biologically inactive optical isomer, was nearly ineffective in releasing PRL. Administration of naloxone, phentolamine, or propranolol did not alter the PRL response to the various test meals, indicating that neither opioid, alpha-adrenergic, nor beta-adrenergic stimulation is involved in meal-induced PRL secretion.

Aspartame and its constituent amino acids: effects on prolactin, cortisol, growth hormone, insulin, and glucose in normal humans.

Because large doses of phenylalanine stimulate prolactin secretion in man, we studied the acute effects of oral doses of aspartame (0.534 g, equivalent to the amount of aspartame in approximately 1 L beverage), aspartic acid (0.242 g), and phenylalanine (0.3 and 1.0 g) on serum prolactin and other hormones in normal humans. Prolactin was not stimulated by any of the aspartame meals, aspartic acid, or 0.3 g phenylalanine; a small rise in serum prolactin, similar to that produced by a high-protein mixed meal, followed ingestion of 1.0 g phenylalanine. Serum growth hormone showed no statistically significant changes in response to any of the experimental meals whereas cortisol and insulin fell slightly and glucose rose slightly during each of the meals. We conclude that these doses of aspartame do not alter secretion of prolactin, cortisol, growth hormone, or insulin in normal individuals.

Desipramine increases circulating growth hormone in elderly depressed patients: a pilot study.

Serial blood samples were collected from 15 elderly depressed inpatients, ages 62 to 95 years, following random assignment to a 50 mg oral test dose of desmethylimipramine (DMI) or amitriptyline (AMI). Nine female and six male subjects began the 210-min study at 0800h. Serum growth hormone (hGH), cortisol, and prolactin (hPRL) were determined by radioimmunoassay. Baseline hormone concentrations were related to self and observer ratings of anxiety and depression. There was a trend for the hGH, cortisol, and hPRL concentrations to decline during the period of study. This trend for all three hormones reversed in those subjects receiving DMI, beginning approximately 90 min after drug ingestion. The DMI-induced increase of hGH reached statistical significance at the very end of the sampling period. There was an apparent latency in the DMI-induced effect for all three hormones. There was no stimulatory effect of AMI on hGH, cortisol, or hPRL. The female subjects had higher baseline hGH levels than the men. In addition, a significant negative correlation was found between baseline hPRL levels and self ratings of anxiety.

Lack of effect of warfarin on L-thyroxine metabolism.

The effect of a single 50 mg dose of warfarin sodium on thyroxine monodeiodination was examined in eight healthy human subjects. There was no evidence that warfarin inhibits 5'-monodeiodination, although such inhibition exists in rats.