Pheochromocytoma.

Causes of hypertension that are amenable to surgical treatment constitute a very small but potentially important segment of the hypertensive population. These causes (which constitute frequently asked questions for medical students) include coarctation of the aorta, aldosterone and corticosteroid-producing tumors of the adrenal glands, lesions producing decreased renal blood flow, and pheochromocytoma. This latter tumor is quite uncommon, with a frequency of roughly one per million, but often produces dramatic hypertensive episodes. Due to its rarity, physicians in practice may not consider the diagnosis and appropriately evaluate the patient. We present the case histories of three patients with pheochromocytoma who demonstrate important features of this disease. Diagnostic evaluation and principles of treatment will be discussed.

Amniotic fluid prolactin in the third trimester of pregnancies complicated by gestational or pregestational diabetes mellitus.

Amniotic fluid concentrations of immunoreactive prolactin were measured during the third trimester in 184 diabetic gravidas and correlated with concurrent levels of prolactin in maternal plasma. Prolactin measurements concorded with previously published estimates in normal gravid women and averaged 825 +/- 32 ng/mL (mean +/- SEM) in amniotic fluid and 168 +/- 6.5 ng/mL in simultaneously sampled plasma. Cross-sectional and longitudinal analyses indicated that the prolactin levels in amniotic fluid of pregnant diabetics declined significantly between weeks 32 and 40 of gestation, whereas plasma levels did not change consistently during the same interval. Mean values for amniotic fluid prolactin did not correlate with simultaneous prolactin concentrations in plasma, nor with maternal age, clinical estimates of polyhydramnios, amniotic fluid creatinine content, or lecithin/sphingomyelin (L/S) ratios or subsequent birth weight of the offspring. Clear-cut correlations with overall maternal glucose regulation could not be demonstrated. However, subtle effects may be operative since amniotic fluid prolactin displayed weak but significant correlations with concurrent levels of maternal plasma glucose, and mean values for hemoglobin A1c (HbA1c) but not with mean values for fasting plasma glucose (FPG). Amniotic fluid prolactin concentrations were significantly greater in patients with pregestational diabetes (White classes C, D, and F) than in women with gestational diabetes mellitus (GDM) (our classes A1, A2, and B1). The differences could not be accounted for by differences in metabolic regulation, maternal age, or weights of these two populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Toleration of head injury by the elderly.

Fifty-six patients 80 or more years of age, admitted because of head injury, provide a clinical profile of the effects of head injury upon an aging population. The mortality rate is high, even in those with good admission Glasgow coma scores. The incidence of intracranial mass hematoma is striking. Falls in the residence constitute the principal mechanism of injury, and preexisting medical conditions are important contributing factors. A significant proportion (60%) of old people may make a full recovery from head injury.

Gestational diabetes mellitus. Correlations between the phenotypic and genotypic characteristics of the mother and abnormal glucose tolerance during the first year postpartum.

We evaluated glucose tolerance during the first year postpartum in 113 women with gestational diabetes mellitus (GDM) diagnosed according to the criteria of the First International Workshop-Conference on GDM and the National Diabetes Data Group. The high incidence of abnormal postpartum glucose tolerance (38% "diabetes mellitus" plus 19% "impaired glucose tolerance") was correlated with certain of the heterogeneous characteristics of the population at the time of antepartum diagnosis. Virtually all women with antepartum fasting plasma glucose (FPG) greater than or equal to 130 mg/dl (GDM class B1) remained abnormal postpartum (21/22 [95%]), which suggests that this group may include women with preexisting glucose intolerance unrecognized before pregnancy. In the remainder, those with FPG greater than or equal to 105-129 mg/dl (GDM class A2) were more likely to be abnormal postpartum than those with FPG less than 105 mg/dl (GDM class A1). Within the A1 and A2 groups, increasing maternal age, relative insulinopenia, and hyperglycemia at 2 h during antepartum OGTT were also associated with a greater likelihood of abnormal glucose tolerance postpartum. The presence of HLA-DR3 and/or -DR4 antigens was not predictive of the status of glucose tolerance during the first year postpartum, although the increased frequency of cytoplasmic islet cell antibodies in A2 and B1 subjects was associated with a high incidence of abnormal postpartum glucoregulation. The high incidence of abnormal postpartum glucose tolerance in all GDM classes makes a compelling case for careful, early, and continuing follow-up of all women with a diagnosis of GDM.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyrotropin-releasing hormone stimulates growth hormone release from the anterior pituitary of hypothyroid rats in vitro.

We have examined the interaction of thyroid hormone and TRH on GH release from rat pituitary monolayer cultures and perifused rat pituitary fragments. TRH (10(-9) and 10(-8)M) consistently stimulated the release of TSH and PRL, but not GH, in pituitary cell cultures of euthyroid male rats. Basal and TRH-stimulated TSH secretion were significantly increased in cells from thyroidectomized rats cultured in medium supplemented with hypothyroid serum, and a dose-related stimulation of GH release by 10(-9)-10(-8) M TRH was observed. The minimum duration of hypothyroidism required to demonstrate the onset of this GH stimulatory effect of TRH was 4 weeks, a period significantly longer than that required to cause intracellular GH depletion, decreased basal secretion of GH, elevated serum TSH, or increased basal secretion of TSH by cultured cells. In vivo T4 replacement of hypothyroid rats (20 micrograms/kg, ip, daily for 4 days) restored serum TSH, intracellular GH, and basal secretion of GH and TSH to normal levels, but suppressed only slightly the stimulatory effect of TRH on GH release. The GH response to TRH was maintained for up to 10 days of T4 replacement. In vitro addition of T3 (10(-6) M) during the 4-day primary culture period significantly stimulated basal GH release, but did not affect the GH response to TRH. A GH stimulatory effect of TRH was also demonstrated in cultured adenohypophyseal cells from rats rendered hypothyroid by oral administration of methimazole for 6 weeks. TRH stimulated GH secretion in perifused [3H]leucine-prelabeled anterior pituitary fragments from euthyroid rats. A 15-min pulse of 10(-8) M TRH stimulated the release of both immunoprecipitable [3H]rat GH and [3H]rat PRL. The GH release response was markedly enhanced in pituitary fragments from hypothyroid rats, and this enhanced response was significantly suppressed by T4 replacement for 4 days. The PRL response to TRH was enhanced to a lesser extent by thyroidectomy and was not affected by T4 replacement. These data suggest the existence of TRH receptors on somatotrophs which are suppressed by normal amounts of thyroid hormones and may provide an explanation for the TRH-stimulated GH secretion observed clinically in primary hypothyroidism.

Inhibitory feedback effects of prolactin on its secretion involve central nervous system dopaminergic mediation.

Feedback regulation of basal and stimulated release of prolactin (Prl) was studied in primary cultures of rat pituitary cells and in adult male rats bearing right atrial catheters. Exposure of cell cultures to ovine (o) Prl, which does not crossreact in the radioimmunoassay for rat (r) Prl, did not affect rPrl release during in vitro incubations. oPrl, 4 mg/kg, injected subcutaneously into male rats 4 h previously, significantly suppressed basal rPrl levels and blunted the rPrl response to ether (2 min), cimetidine (25 mg/kg i.v.), thyrotropin-releasing hormone (40 or 400 ng i.v.), or a low dose of metoclopramide (25 micrograms/kg i.v.). At a higher dose of metoclopramide (500 micrograms/kg i.v.), no effect of oPrl could be observed. These data support the hypothesis that Prl feedback control occurs within the central nervous system rather than at the pituitary and involves predominantly, if not exclusively, a dopaminergic mechanism.

Daily rhythm of plasma melatonin in normal and precocious puberty.

A previous study of normal humans has shown a decrease in plasma melatonin at the onset of puberty, suggesting that melatonin may act to restrain pubertal onset. We have measured plasma melatonin throughout a 24-h period in normal and constitutionally short males at different pubertal stages and in patients with idiopathic true precocious puberty and familial male isosexual precocity. The 24-h profile of plasma melatonin was similar for the prepubertal, pubertal, and adult males studied, with all subjects having low levels (20-50 pg/ml) during the day and high levels (80-100 pg/ml) at night between 0100-0500 h. The 24-h profiles of the patients with isosexual precocity were similar to the profiles observed throughout normal puberty. These data do not support a role for melatonin in the initiation of normal or precocious puberty in man.

Autonomous thyroid nodules in adolescents: clinical characteristics and results of TRH testing.

Seven adolescents with autonomous thyroid nodules were evaluated over a three-year period. They had hyperfunctioning nodules on radionuclide scan which failed to suppress with exogenous administration of thyroid hormone. They were clinically euthyroid and had normal T4, free T4, and basal TSH values. However, as a group they had elevated total serum T3 concentrations, blunted TSH response to TRH, and accelerated closure of cranial sutures, all of which suggested subtle hyperthyroidism. These patients have been followed for one to five years. Four have undergone partial thyroidectomy because of persistent elevation in the serum T3 concentration or enlargement of the nodule. The clinical presentation and laboratory findings in this group are similar to those found in adults with autonomous nodules.

Failure of bromocriptine to lower plasma catecholamines in normal men and women.

A plasma catecholamine-lowering effect of bromocriptine has previously been reported in normals, but not in patients with PRL- or GH-secreting pituitary tumors, and has been used as evidence to support the concept of disordered central nervous system dopaminergic tone in patients with such tumors and as a test to distinguish them from normals. In the present study of 16 normal subjects (9 women and 7 men), we found no significant change in plasma norepinephrine or epinephrine after bromocriptine. Similarly, no change occurred in plasma catecholamines in 8 patients with PRL-secreting tumors or 6 patients with ACTH hypersecretion. Our data, therefore, do not provide confirmatory evidence for an effect of bromocriptine on plasma catecholamines in normal subjects and do not support the proposed use of bromocriptine as a test for defective central dopaminergic regulation.

Thyroid hormone homeostasis in states of relative caloric deprivation.

Starvation is accomplished by significant changes in the hypothalamic-pituitary-thyroid axis and in peripheral thyroid hormone metabolism. Less well studied, however, are the effects on thyroid hormone economy produced by hypocaloric feeding. We explored these changes in obese patients fed 200, 400, or 600 cal/day of either carbohydrate of protein for 28 days. T4' T3' reverse T3 and the TSH response to TRH were measured at frequent intervals. Each patient demonstrated a transient rise in reverse T3 and a fall in T2 that returned to near basal levels by the end of the study period. The TSH response to TRH on the other hand, declined to approximately 50% of control values and remained at that level throughout the course of study, regardless of the type of substrate or calorie level chosen. The results indicated that hypocaloric feeding is associated with changes in thyroid hormone economy similar to those in starvation and that peripheral (changes in T3 and rT3) and central (TRH response) events are controlled by separate mechanisms.

Somatostatin effects on lower esophageal sphincter function.

The effect of somatostatin (GH-RIH) infusion (2 microgram/min) on lower esophageal sphincter pressure (LESP) responses to various stimuli was evaluated in adult male baboons. GH-RIH infusion did not affect basal LESP, but did cause a significant suppression of mean immunoreactive insulin (IRI) to 5.8% of basal values (P less than 0.05). Pentagastrin IV caused dose-related increases in LESP that were unaffected by GH-RIH. Abdominal compression caused a threefold rise in LESP (P less than 0.005) both without and with GH-RIH. However, atropine (20 microgram/kg iv bolus) completely blocked this cholinergic LES pressure response. Intragastric alkali as well as intragastric glycine caused significant increases in LESP (P less than 0.05). These LESP responses to alkali and to glycine were totally abolished by GH-RIH. In conclusion, GH-RIH infusion in the baboon does not affect basal LESP, LES smooth muscle response to exogenous stimulation, nor a cholinergically mediated LES response. GH-RIH does inhibit the response of LESP both to intragastric alkali and to glycine by the apparent suppression of a hormonally mediated mechanism.

Exercise tolerance test. Single-sample screening technique to rule out growth-hormone deficiency.

Parent-directed vigorous exercise was evaluated as a screening test for adequacy of pituitary growth-hormone release in 57 short-statured children. This method obviated the need for pharmacologic provocative testing in all but the four children with growth-hormone deficiency. In 92% of the euendocrine children, the immediate postexercise venous sample demonstrated an adequate growth-hormone level. Vigorous physical exercise after an 8- to 12- hour fast with a single postexercise serum growth-hormone sample is a reliable, safe, and cost-effective screening test for growth-hormone deficiency.