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The actuarial risk for developing benign or malignant thyroid disease following radiation therapy (RT) is controversial, but may be as high as 50% at 20 years. An effective screening modality should be specific but not overly sensitive, a limitation of ultrasound. We questioned whether Technetium-99 m pertechnetate ((99m)Tc TcO(4)(-)) scanning could detect clinically significant disease in ostensibly disease-free cancer survivors.Eligibility criteria included an interval of at least 5 years after RT to the cervical region, a thyroid gland that was normal to palpation, euthyroid status determined by clinical examination, free T4 and TSH. The 34 patients scanned included 16 children (18 years old) and 18 adults at the time of RT, 16 females and 18 males. The mean age at RT was 20 years (range, 2.1-50.3 years), and the mean age at (99m)Tc TcO(4)-scanning was 33 years (range, 13.6-58 years), providing a mean interval of 13 years (range, 5.3-26.6 years). The mean RT dose to the thyroid was 36.4 Gy (range, 19.5-52.5). Thyroid scanning was performed with a 5 mCi dose of (99m)Tc TcO(4)(-) obtaining flow, immediate and delayed static, and pinhole collimator images.Seven patients (21.6%) had abnormal scans, and the percentage was higher among children (25%) and females (25%) compared to adults (16.7%) and males (16.7%), respectively. Two of 34 patients (5.9%) were discovered to have a thyroid cancer; histopathologies were papillary and follicular carcinoma.In this population of clinically normal cancer survivors who had been irradiated to the cervical region, subclinical thyroid disease, of potential clinical significance, was detected by (99m)Tc TcO(4)(-) in about 20%. Children may be more commonly affected. Although the cost effectiveness of screening will require a larger sample number, we propose a surveillance schema for this patient population.

Objective: To study the changes in neuroautonomic regulation of heart rate and the effects of N G -nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of nitric oxide synthase, on efferent sympathetic cardiac activity and blood pressure during hypovolemic shock. Hypotension during hypovolemic shock may be attributable, in part, to the failure of neuroautonomic regulation of heart rate and blood pressure. In addition, the release of nitric oxide may contribute to hypotension through vasodilation and inhibition of efferent sympathetic activity. Design: Prospective, controlled trial. Setting: Experimental laboratory in a university hospital. Subjects: Seventeen anesthetized adult male New Zealand White rabbits. Interventions: The rabbits were divided into four groups: control (n = 3), control plus L-NAME (n = 5), hypovolemic (n = 4), and hypovolemic plus L-NAME (n = 5). Hypovolemic rabbits were bled of 10% of their circulating blood volume (85 mL/kg) every 10 mins until 30% cumulative hypovolemia was reached. Rabbits received either three doses of saline 1 mL/kg every 10 mins or L-NAME 10 mg/kg in 1 mL/kg of saline solution administered after each hemorrhage for a total of three doses. Changes in heart rate, respiratory rate, mean arterial pressure, plasma catecholamine levels, and heart rate power spectra were recorded every 10 mins during serial hypovolemia and during a 30-min recovery period. Measurements and Main Results: During hypovolemic shock there was a decrease in log low-frequency heart rate power (p = .001) and in systolic (p = .003), diastolic (p

Gram-negative septic shock is associated with severe hypotension and autonomic cardiovascular dysfunction. We hypothesized that in an anesthetized rabbit model of endotoxin shock, autonomic modulation of cardiac activity, as measured by power spectral analysis of heart rate (HR) variability, would be decreased compared with the anesthetized control rabbits.Experimental, comparative study.Laboratory of a university hospital.Fourteen adult male New Zealand white rabbits (2.7 to 3.1 kg body weight) were studied under anesthesia.None.We studied the absolute and temporal changes in HR power spectra and plasma catecholamine concentrations in eight experimental and six control New Zealand white rabbits during Escherichia coli endotoxin-induced shock. HR, respirations, arterial blood pressure (BP), HR power spectra, and plasma catecholamine concentrations were measured at 5- to 10-min intervals for 60 mins in control rabbits or until the mean arterial pressure (MAP) decreased byor = 20 mm Hg in experimental rabbits. There were no differences in basal HR, respiratory rate, BP, HR power spectra, or catecholamine concentrations between groups. After endotoxin administration, MAP decreased (82 +/- 7 vs. 62 +/- 5 mm Hg; p.05) as did log low-frequency HR power (-2.14 +/- 2.46 vs. -2.20 +/- 2.48 beats/min2; p.05). Low-frequency HR power and MAP remained unchanged in control animals. Log high-frequency HR power decreased in control and experimental rabbits (-1.02 +/- 1.34 vs. -1.69 +/- 2.12 [control], p.05; -1.53 +/- 2.19 vs. -2.19 +/- 2.85 beats/min2 [experimental], p.05). While there was an inverse relationship between low- and high-frequency HR power and MAP, the direction of change was opposite in six of six rabbits in the control group and in six of eight rabbits in the experimental group. Plasma catecholamine concentrations did not change during the experiment in either group.Sympathetic modulation of cardiac activity decreased, while the sympathomedullary response remained unchanged during endotoxin shock. We speculate that a concomitant decrease in low-frequency HR power as MAP decreases may prove to be an early marker for impending shock.

Background. Small cell carcinoma (SCC) associated with clinical evidence of tumor corticotropin (ACTH) production is common, and management of this syndrome is difficult. The purpose of this retrospective analysis is to describe clinical features, prognosis, and treatment results in patients with SCC and the syndrome of ectopic ACTH secretion to permit formulation of management guidelines for these patients. Methods. Using tumor registry data and chart review, the authors identified patients with SCC and ectopic ACTH secretion treated over 11 years at two large teaching hospitals. They recorded clinical and laboratory data regarding the patients' tumors and their endocrine syndrome along with results of treatment for the malignancy and the hypercortisolism. Results. Ten patients with SCC and ectopic ACTH secretion were identified. These patients were initially seen with adverse prognostic features, including elevations of serum lactate dehydrogenase and extensive stage disease. Cytotoxic chemotherapy and standard doses of antiadrenal medications rarely controlled the paraneoplastic syndrome. Bacterial or opportunistic infections, although not neutropenic, developed in most patients. Median survival of patients diagnosed with the paraneoplastic syndrome at the same time as the initial diagnosis of cancer was 4 months. However, three patients whose cortisol secretion was controlled survived longer than 6 months. Conclusions. Patients with SCC and ectopic ACTH syndrome have a poor prognosis. However, in the minority of patients whose hypercortisolism can be controlled with cytotoxic chemotherapy combined with treatment to inhibit cortisol biosynthesis, effective palliation can be achieved. Cancer 1994; 73:1361–7.

Patients with brain tumors who are treated with radiation frequently have growth hormone deficiency, but other neuroendocrine abnormalities are presumed to be uncommon.We studied endocrine function in 32 patients (age, 6 to 65 years) 2 to 13 years after they had received cranial radiotherapy for brain tumors. The doses of radiation to the hypothalamic-pituitary region ranged from 3960 to 7020 rad (39.6 to 70.2 Gy). Nine patients also received 1800 to 3960 rad (18.0 to 39.6 Gy) to the craniospinal axis. Serum concentrations of thyroid, gonadal, and pituitary hormones were measured at base line and after stimulation.Nine patients (28 percent) had symptoms of thyroid deficiency, and 20 patients (62 percent) had low serum total or free thyroxine or total triiodothyronine concentrations. Of the 23 patients treated only with cranial radiation, 15 (65 percent) had hypothalamic or pituitary hypothyroidism. Of the nine patients who also received spinal (and thus direct thyroid) radiation, three (33 percent) had evidence of primary thyroid injury. Seven of the 10 postpubertal, premenopausal women (70 percent) had oligomenorrhea, and 5 (50 percent) had low serum estradiol concentrations. Three of the 10 men (30 percent) had low serum testosterone concentrations. Overall, 14 of the 23 postpubertal patients (61 percent) had evidence of hypogonadism. Mild hyperprolactinemia was present in 50 percent of the patients. Responses to stimulation with corticotropin-releasing hormone and corticotropin were normal in all patients except one, who had panhypothalamic dysfunction. However, serum 11-deoxycortisol responses to the administration of metyrapone were low in 11 of the 31 patients (35 percent) tested. Three of the 32 patients, (9 percent) had no endocrine abnormalities, 9 (28 percent) had an abnormal result on tests of thyroid, gonadal, prolactin, or adrenal function, 8 (25 percent) had abnormalities in two axes, 8 (25 percent) in three axes, and 4 (12 percent) in all four axes.Cranial radiotherapy in children and adults with brain tumors frequently causes abnormal hypothalamic-pituitary function. The most frequent changes are hypothyroidism and gonadal dysfunction, although subtle abnormalities in adrenal function may also be present.

To study and compare the autonomic cardiovascular state of children after severe brain injury and brain death.Prospective clinical study.Pediatric ICU.Pediatric patients suffering severe brain injury caused by trauma, anoxia, or hemorrhage.None.We analyzed cardiorespiratory parameters, heart rate power spectra, plasma catecholamine concentrations, and the response to the cold pressor test in nine brain-dead patients and compared the results with the test findings of 11 patients with severe brain injury. Low-frequency total heart rate power (p.03), peak amplitude (p.02), and plasma catecholamine concentrations (p.001) were different with no overlap of values between groups. Cold pressor testing in patients with severe brain injury showed changes in respiratory rate and low-frequency heart rate power that were +/- 20% to 100% from baseline values; however, there were no measurable changes in brain-dead patients.Our results support the concept of a damaged sympathetic cardiovascular system in severe brain injury and complete interruption of the autonomic cardiovascular pathways in brain death. Since determination of brain death may be difficult, our findings have implications for corroborating brain death using autonomic cardiovascular testing.

To review the hormonal changes that have been reported after trauma, to define their etiologies, and to describe their consequences.Literature review using MEDLINE and original data.Hormonal responses to trauma are bidirectional. Functional derangements include increases in adrenocorticotropin hormone and cortisol, growth hormone, and prolactin levels. In contrast, gonadotropin and gonadal steroid, and thyroid hormone concentrations decrease. The response is immediate but not necessarily sustained for those hormones that respond with increased secretion, whereas the effect may not become apparent for several hours, may be maximal after 1 to 4 days, and may persist for the duration of illness for those hormones that decrease. The reduction in hormone concentrations generally reflect diminished secretion, with the exception of the thyroid hormones where altered metabolic pathways and enhanced metabolic clearance play a major role.The changes in circulating levels do not appear to be injury specific, but tend to reflect the severity of the traumatic insult, and there are some data for cortisol and thyroxine that show their concentrations may be of predictive value. In head-injured patients, structural as well as functional pituitary changes may be present. Patients may show varying degrees of pituitary insufficiency. However, the presence of hyperprolactinemia strongly suggests involvement of the hypothalamus. With the exception of bonafide hypopituitarism, the relevance of the hormonal changes after trauma awaits clarification.

To report a unique case of a patient with multiple head and neck tumors following treatment for craniopharyngioma. Retrospective review of the medical record. There is an association between radiation treatment for primary intracranial malignancies and the subsequent development of other intracranial tumors. At the same time, reports regarding the association between thyroid cancer and radiation exposure are abundant within the literature. We present a unique case of a young female who underwent resection and radiation treatment for a craniopharyngioma in 1988. With the exception of bitemporal visual loss and panhypopituitarism requiring hormone replacement therapy, the patient had a relatively uneventful course until 2005. At that time, she developed hearing loss and incapacitating vertigo, which was ultimately attributed to a temporal bone Langerhans histiocytosis. A year and a half later, she was noted to have a thyroid nodule, the pathology of which revealed papillary carcinoma. Seven months after that, she developed new auditory and vestibular symptoms attributable to an acoustic neuroma. This case is remarkable because neither Langerhans histiocytosis following radiation of a craniopharyngioma nor this distinctive combination of head and neck tumors in general have ever been previously reported.

Clinical thyrotoxicosis is rare in molar pregnancy and has yet to be reported in a patient with a partial mole. Human chorionic gonadotropin (hCG), which has thyrotropic activity, is believed to be responsible for hyperthyroidism of gestational trophoblastic activity and hyperemesis gravidarum. We report the first case of hyperthyroidism presenting as thyroid storm in a partial molar pregnancy. Normal thyroid function returned after the partial mole was evacuated, and the biochemical improvement correlated with declining hCG levels. This case highlights the importance of including partial mole in the differential of hCG-mediated hyperthyroidism.

To test the hypothesis that cortisol levels reflect the extent of neurologic dysfunction and predict patient outcome, neurologic function and cortisol levels were determined in 120 traumatically brain injured patients who never received glucocorticoid treatment. Their mean age was 29 years and 78% were men. The impact of intoxication was examined in 59 patients who had ethanol levels measured. Ethanol was detectable in 40 patients and greater than or equal to 100 mg/dl in 31. There were significant correlations between the extent of neurologic dysfunction, determined by the Glasgow Coma Score and plasma cortisol concentrations 1 and 4 days postaccident. Cortisol levels were universally elevated on admission and approached normal 7 days later. Multiple linear regression analysis revealed significant effects of circulating ethanol levels on the association between cortisol concentrations and progressively worsening neurologic function, i.e., ethanol reduced the magnitude of the cortisol elevations in a dose dependent manner, abolishing this relationship at levels above 100 mg/dl. Analysis of the relationships between circulating cortisol levels and patient outcome provided a second method for ascertaining the association between injury severity and the magnitude of adrenocortical activation. Admission and day 1 cortisol concentrations were 25 to 40% lower in patients having good recoveries or moderate disabilities than those who remained severely disabled, persistently vegetative or died; serum cortisol values of less than 20 micrograms/dl one day after the accident were more likely to be associated with a good outcome than a poor one (55 vs. 25%, p less than 0.001). The worsening prognosis of patients having higher cortisol values is further reflected in the duration of acute hospitalization of these individuals.(ABSTRACT TRUNCATED AT 250 WORDS) Language: en

Pituitary hyperplasia secondary to primary hypothyroidism has been reported in the literature in both adults and children. We report a case of a young woman who was diagnosed with hypothyroidism in her teenage years. Despite frequent follow-up, her TSH levels remained greater than 100 mIU/ml. A few years later, pituitary enlargement was found on an MRI at a time when her TSH was 177 mIU/ml and her free T4 was 0.2 ng/dl. Observed administration of 600 mcg of L-thyroxine was performed to determine the effectiveness of hormone absorption. Total T4 levels of 0.2 rose to 7.1 mcg/dl at two hours with a decrease in her TSH levels from 88.6 to 66.8 mIU/ml at 24 hours. With the exception of one short period, her TSH levels have remained elevated over eight years of observation without change in the size of the pituitary mass. In our review of the literature, primary uncontrolled hypothyroidism has been described as a precursor to pituitary hyperplasia. In these patients, TSH-secreting adenomas were distinguished from pituitary hyperplasia by a blunted TRH stimulation test, elevated alpha subunit concentration values, and elevated alpha subunit concentration/TSH ratios. TSH levels ranged from 98 to 732 mIU/ml in adults, and even higher values in children. Following adequate hormone replacement with L-thyroxine doses of 25 to 300 mcg/day, both symptoms and pituitary hyperplasia regressed on average within a few months.

The incidence and pattern of changes in thyroid function tests were studied in acutely hospitalized psychiatric patients and the cost effectiveness of a systematic screening program for thyroid dysfunction was estimated. Thyroid testing was performed on 1275 of 1424 (90%) admissions to the psychiatric wing of Strong Memorial Hospital between April 1, 1993 and March 30, 1994. Discharge samples were obtained in 232 patients who were hospitalized at least 2 days; 163 patients were admitted multiple times. Psychiatric diagnosis was coded using DSM-III-R criteria. TSH, T4, free T4, and T3 levels were measured within 48 h of admission. TSH values were most frequently abnormal (7.8%) and free T4 the least (1.3%). Admission and discharge thyroid tests were similar. Significant differences in the four parameters of thyroid function were present among the psychiatric groups. By analysis of variance every 1 microU/mL increase in TSH levels was associated with a 2.5% increase in length of stay (LOS) (95% confidence intervals: 0.21%, 4.75%), holding psychiatric diagnosis, age, and gender constant. For patients with elevated TSH levels, the average LOS was increased by 10.7 days (95% confidence intervals: 2.8, 18.7 days). It is concluded that patients hospitalized for psychiatric illness have an incidence of thyroid dysfunction at or slightly higher than the general population. However, patients with elevated TSH levels are hospitalized longer than those with normal or suppressed values.

To study sequential changes in heart rate, respiratory rate, blood pressure, heart rate power spectra, and plasma catecholamine concentrations in patients with acute brain injury and correlate these variables with the severity of neurologic dysfunction and patient outcome.Prospective, clinical study.Pediatric intensive care unit.Thirty-seven pediatric patients with acute brain injury caused by trauma, anoxia/ischemia, hemorrhage, or infection.None.We found significant associations between low-frequency (0.01 to 0.15 Hz) heart rate power and severity of neurologic dysfunction (as assessed by the admission Glasgow Coma Scale) (p.001) and patient outcome (as assessed by the Glasgow Outcome Scale) (p = .05). The admission (p = .05) and maximum (p.001) values for low-frequency heart rate power and the minimum value for high-frequency (0.15 to 0.50 Hz) heart rate power obtained during hospitalization (p = .001) predicted an increased likelihood of survival. Ten brain-dead patients had significantly decreased low-frequency heart rate power (p = .008) and plasma norepinephrine (p = .015), epinephrine (p = .03), and dopamine (p = .04) concentrations when compared with six non-brain-dead patients with a Glasgow Coma Scale score of 3.Our results imply that autonomic nervous system control of heart rate is disrupted in proportion to the degree of neurologic insult in children after acute brain injury. Thus, heart rate power spectral analysis and plasma catecholamine concentrations may prove to be useful adjuncts in determining severity of neurologic injury and prognosis for recovery in children suffering from brain injury. In addition, these techniques may aid in the determination of brain death.

Objective. The purpose of this study was to determine the effects of naloxone on systemic hemodynamics and reflex function in dogs with congestive heart failure induced by rapid pacing. Background. We have shown previously that naloxone, an opiate receptor antagonist, improves cardiac output, aortic blood pressure, systolic performance and the baroreflex function in conscious dogs with chronic right-sided congestive heart failure. However, whether endogenous opioids also play a role in mediating the reduction of myocardial and baroreflex function in animals with left heart failure remains controversial. Methods. We administered naloxone (1 mg/kg body weight) and normal saline solution to 15 dogs with pacing-induced congestive heart failure (225 beats/min for 8 weeks) and 11 control dogs. In addition to systemic hemodynamic measurements, the slope of pressure-area relation obtained from echocardiography with intravenous bolus injection of phenylephrine was taken as a load-independent index of myocardial contractility. Baroreflex function was estimated by the slope of the regression line relating systolic aortic pressure and RRE interval. Results. Plasma beta-endorphin levels were elevated in dags with congestive heart failure. Naloxone administration increased heart rate, mean aortic pressure, first derivative of left ventricular pressure, cardiac output and myocardial contractility in pacing-induced congestive heart failure. These changes correlated significantly with basal plasma beta-endorphin levels and were accompanied by increases in plasma beta-endorphin and catecholamines after naloxone administration. However, unlike the hemodynamic and cardiac effects of naloxone, baroreflex function did not change after naloxone in dogs with congestive heart failure. Conclusions. The increase in basal plasma beta-endorphin suggests that the endogenous opiate system is activated in lef-tsided congestive heart failure. Because naloxone improves the systemic hemodynamics and myocardial contractile function under this condition, the endogenous opioids appear to play an important role in mediating the myocardial depression that occurs in heart failure. However, the endogenous opiate system has no apparent effect on the regulation of baroreflex control in heart failure induced by rapid pacing.

• We studied the catecholamine response in two groups of patients with multisystem injuries according to the presence (group 1, N=124) or absence (group 2, N=82) of head injury. Markers of injury severity included the Injury Severity Score, the Glasgow Coma Scale, the need for intubation, admission hypotension, the amount of blood products and fluid expanders administered during the first 24 hours, and patient outcome. In group 1, higher norepinephrine levels always and epinephrine concentrations usually were associated with worsening indexes of injury severity. The best correlations were between the Injury Severity Score and the Glasgow Coma Scale and norepinephrine concentrations. In group 2, despite elevated catecholamine levels, such associations were seldom present. Thus, circulating catecholamine levels, especially norepinephrine levels, significantly correlated with the severity of injury in patients who had suffered multisystem injury, but only if the injury included the brain. ( Arch Surg . 1992;127:899-903)

In patients suffering isolated head trauma, we have previously shown that levels of circulating catecholamines obtained within 48 hours of trauma correlate with the severity of brain injury and predict outcome and that intoxication blunts this response. The effects of alcohol on the increase in catecholamines in systematically injured patients, however, have not been well defined. From 1983 to 1990, 78 patients (74% male; median age 30 years) with blunt head and multisystem injury, who also had alcohol levels measured within 5 hours of injury, were studied. Norepinephrine and epinephrine levels were assayed by a radioenzymatic technique. Injury severity was assessed by the admission Glasgow Coma Scale (GCS) score (4-15; median, 12), the Injury Severity Score (ISS) (13-50; median, 25) and the volume of blood products administered within the first 24 hours (0-14.4 L; median, 0.5 L). The impact of alcohol on the norepinephrine response to injury was analyzed using multiple linear regression models, including polynomial interaction terms. Norepinephrine levels significantly (p less than 0.0001) correlated with the GCS score and ISS. However, alcohol significantly lowered the norepinephrine response to decreasing GCS score (R = 0.49, p less than 0.002) and to increasing ISS (R = 0.51, p less than 0.0006). The blunting of the catecholamine response was most marked in those severely injured. The rise in norepinephrine concentrations seen with increasing volume of blood replacement was not affected by intoxication. An association between injury severity and epinephrine levels was also present, but not as consistently. Epinephrine concentrations rose with falling GCS score and with increasing ISS values, but unlike norepinephrine, there were no apparent effects of alcohol on changes in epinephrine levels. Thus, in patients suffering head and multisystem injury, catecholamine changes reflect the severity of injury using three different scalers. Furthermore, intoxication blunts only the norepinephrine component of this important biologic response.

In 46 patients experiencing traumatic brain injury, we studied the interactions of alcohol intoxication and severity of neurologic dysfunction on the resulting sympathetic nervous system activation. Sixty percent of the variation in norepinephrine (p less than 0.0001) and more than 50% of the variation in epinephrine (p less than 0.0001) were due to the initial ethanol concentrations and extent of brain injury assessed by the admission Glasgow Coma Score (GCS). As brain function deteriorated plasma cathecholamines rose (p less than 0.0001), but ethanol qualitatively and quantitatively modified this observation. The magnitude of the sympathetic response to worsening neurologic function was progressively diminished in association with increasing ethanol levels, i.e., the inverse relationship of GCS values with both norepinephrine and epinephrine was flattened. In comatose patients (GCS less than 8) increasing ethanol levels was associated with progressively decreasing norepinephrine and epinephrine responses (p less than 0.04), such that catecholamines were reduced by 80 to 90% at ethanol concentrations approaching 400 mg/dl (87.0 mmol/l). However, the impact of ethanol on the degree of sympathetic nervous system activation depended upon the degree of injury; the apparent ethanol suppression was greatest in patients with the most severe neurologic dysfunction (GCS 3 or 4), but it diminished as neurologic function improved. We conclude that the presence of alcohol appears to modify the rise in catecholamine levels following traumatic brain injury in a dose-dependent manner and alters the relationship between neurologic dysfunction and SNS activation. These alterations may have profound effects on patient morbidity in the immediate post-accident period. Language: en

The effects of acute severe illness on pituitary-gonadal function were determined in 35 men and 19 women, including 12 who were postmenopausal. Seventeen men and 5 women had traumatic brain injury which resulted in coma. Twelve postmenopausal and 2 premenopausal women had intracranial vascular accidents. Eleven men had myocardial infarctions, while 7 men underwent elective surgery. Serial plasma samples were examined for testosterone (men), percentage of ultrafiltrable testosterone (men), estradiol (women), sex hormone-binding globulin, LH, and FSH. In men, mean testosterone levels fell by 271 +/- 72 (+/- SE), 202 +/- 63 and 195 +/- 75 ng/dl within 24 h of brain injury, myocardial infarction, or elective surgery, representing decreases of 55%, 43%, and 58%. Further declines occurred in the first and third groups to mean nadirs of 93 +/- 16 and 117 +/- 5 ng/dl, respectively. During recovery of neurological function there was no correlation between the testosterone level and the degree of neurological impairment; testosterone levels eventually returned to normal (627 +/- 77 ng/ml). The percentage of ultrafiltrable testosterone and sex hormone-binding globulin did not change in any group. Although significant decreases in mean immunoreactive LH and FSH levels were found after head trauma, and decreases in FSH were found in the men after surgery, these changes occurred after the decline in testosterone. Despite the fall in basal gonadotropin levels in the head trauma group, there were no significant differences in the gonadotropin responses to GnRH (100 micrograms) in 4 patients during their acute illness or recovery. LH, FSH, and estradiol levels in the premenopausal women were significantly lower on the second day of brain injury (LH, 10.3 +/- 4.7 vs. 3.5 +/- 0.6 mIU/ml; FSH, 3.8 +/- 1.9 vs. 1.4 +/- 0.8 mIU/ml, estradiol, 200 +/- 41 vs. 102 +/- 16 pg/ml) and remained suppressed for 7 days. Gonadotropin levels also fell in the postmenopausal women within 24 h; reductions in LH of 74% and in FSH of 62% were present by day 7 of study. We conclude that both men and women who are critically ill uniformly develop temporary hypogonadotropic gonadal insufficiency regardless of their illness. In men, it is manifested by low testosterone levels, while a comparable decrease in estradiol is present in women. The low testosterone concentrations are not due to reduced sex hormone-binding capacity. Based upon our data in postmenopausal women, hypogonadotropism also occurs in the presence of nonfunctioning gonads. Although our studies do not completely establish the pathophysiology of this disorder, they suggest a suprapituitary origin.

Endocrinologic dysfunction including hyperprolactinemia and hypothyroidism are recognized complications of irradiation to the hypothalamic-pituitary axis or thyroid gland in the course of treating CNS malignancies. However, the frequency of these adverse effects in both short- and long-term survivors may be underestimated. Sixty-five patients treated in the University of Rochester Cancer Center since 1968 with radiation with or without BCNU chemotherapy for CNS tumors not involving the hypothalamic-pituitary axis were evaluated for thyroid, prolactin, and gonadal disturbances regardless of clinical symptomatology. Prolactin values were elevated in 19 of 47 patients (40%). For males and females treated with greater than 55 Gy, abnormal values were present in nine of 11 (82%) and seven of 14 (50%), respectively. For males and females treated with less than or equal to 55 Gy, two of nine (22%) and one of 13 (8%), respectively, were abnormal (P = .0001). Six of six patients who also received BCNU chemotherapy were hyperprolactinemic, as compared with six of ten (60%) who did not receive BCNU. Seven of eight females with elevated prolactin levels had menstruation abnormalities, and five of seven adult males noted a decrease in libido. Mild abnormalities in testosterone concentration were found in three of nine men evaluated, all of whom had normal gonadotropins. Of 47 patients who did not receive irradiation to the spinal axis (and thus the thyroid gland), ten (21%) had a decreased thyroxin (T4) value. Only one of these patients had an elevated thyroid-stimulating hormone (TSH) value. Of 32 patients who received greater than 55 Gy, ten (31%) had a low T4, compared with zero of 15 who received less than or equal to 55 Gy (P = .0001). Four of eight patients (50%) who also received BCNU had low T4 values, as compared with three of 14 (21%) who did not receive BCNU. Of 15 patients who were treated with 4 to 10 MV photon irradiation to the spinal axis, five patients (33%) had elevated TSH values. The mean spinal axis dose in these patients was 33 Gy. Two euthyroid children in this group manifested the early onset of puberty. The complex of endocrinologic abnormalities observed in several patients receiving only cranial irradiation, that is elevated prolactin, decreased thyroid, and gonadal hormone secretion in the presence of otherwise normal pituitary hormone levels, suggests a radiation-induced insult to the hypothalamic regulation of pituitary function.

Although the role of the neurotransmitter, dopamine (DA), in the regulation of PRL has been well documented, controversy exists regarding its participation in the regulation of the other pituitary hormones. Consequently, we infused DA into six healthy male subjects (ages 19-32) and studied its effects on both basal pituitary hormone levels and augmented hormonal release induced by insulin hypoglycemia (ITT), TRH, and gonadotropin-releasing hormone (GnRH). DA alone produced a modest though significant increase in GH concentration from 2.2 +/- 0.5 to 11.9 +/- 3.7 ng/ml (P less than 0.05) by 60 min, but the peak incremental GH response to ITT was significantly inhibited by DA (43.5 +/- 5.0 vs. 16.3 +/- 3.3 ng/ml; P less than 0.01). PRL concentrations fell during the DA infusion (20.4 +/- 3.0 to 10.6 +/- 1.5 ng/ml; P less than 0.02) at 235 min, and the PRL responses to both ITT and TRH were completely abolished. Although the basal LH and FSH concentrations were unaffected by DA, the incremental LH response to GnRH was inhibited (45.5 +/- 10.6 to 24.4 +/- 5.4 mIU/ml; P less than 0.05), while the FSH response was unchanged. DA significantly reduced the basal TSH concentration from 3.9 +/- 0.2 to 2.5 +/- 0.2 micro U/ml (P less than 0.01) at 230 min and blunted the peak incremental TSH response to TRH (6.0 +/- 1.5 vs. 2.9 +/- 0.9 microU/ml; P less than 0.01). DA had no effect on basal cortisol levels, the cortisol response to ITT, basal plasma glucose, or the degree of hypoglycemia after ITT. Our data provide new evidence that DA has an inhibitory as well as a stimulatory role in the regulation of GH secretion in normal humans. It inhibits centrally as well as peripherally mediated PRL secretion and blunts the LH response to GnRH. In addition, DA lowers both basal and TRH-mediated TSH release, confirming the reports of other investigators.

The site, hypothalamic and/or pituitary, for dopaminergic inhibition of prolactin (PRL) secretion is unknown. Consequently, the effect of central dopamine (DA) augmentation on stimulated PRL release was determined in 5 healthy men. Regular insulin (o.1 U/kg i.v.), a potent central stimulus for PRL secretion, and TRH, a direct hypophyseal stimulus, were given alone or one hour after the third and fourth doses, respectively, of L-dopa plus the peripheral decarboxylase inhibitor, carbidopa (Sinemet 20/200 or 25/250 every 6 hours). PRL increased from 26.6 +/- 5.8 to 48.8 +/- 5.2 ng/ml (p less than 0.01) 40 minutes after insulin administration. In contrast, during Sinemet therapy the hypoglycemia-mediated PRL release did not occur, and the PRL levels were significantly lower than after insulin alone from 40 through 180 minutes. Following TRH, neither the maximal PRL rise (69.3 +/- 3.2, TRH alone vs 48.7 +/- 19.8 ng/ml, TRH + Sinemet) nor the maximal increment (37.5 +/- 5.5 vs 29.9 +/- 20.3 ng/ml) was significantly affected by Sinemet. It is concluded that central DA augmentation abolishes central but not peripherally mediated PRL release.

✓ Because of the central role of the sympathetic nervous system in mediating the stress response, plasma norepinephrine (NE), epinephrine (E), and dopamine (DA) levels were measured in 61 traumatically brain-injured patients to determine whether catecholamine (CA) levels obtained within 48 hours after injury provide reliable prognostic markers of outcome. Patient outcome was determined at 1 week using the Glasgow Coma Scale (GCS) and at the time of discharge using the Glasgow Outcome Scale (GOS). Levels of NE, E, and DA correlated highly with the admission GCS score (NE: r = 0.58, p < 0.0001; E: r = 0.46, p < 0.0025; DA: r = 0.27, p < 0.04). Moreover, in the 21 patients with GCS scores of 3 or 4 on admission, NE levels predicted outcome at 1 week. All six patients with NE levels less than 900 pg/ml (normal level less than 447 pg/ml) improved to GCS scores of greater than 11, while 12 of 15 with NE values greater than 900 pg/ml remained with GCS scores of 3 to 6 or died. Levels of E and DA were not as useful. Catecholamine levels also increased significantly as the GOS score worsened. Levels of NE and E were significantly higher in patients who died or remained persistently vegetative than in those with better outcomes. In the 54 patients who survived beyond 1 week, significant correlations were present between the length of hospitalization and NE (r = 0.71, p < 0.0001) and E (r = 0.61, p < 0.0001) levels. Concentrations of NE (r = 0.61, p < 0.0004) and E (r = 0.48, p < 0.01) were also highly correlated with the duration of ventilatory assistance. Analysis of the interactions of CA levels and GCS scores, duration of ventilatory assistance, and length of hospitalization revealed that the CA's either enhanced the reliability of the GCS score or were independent predictors of outcome. Thus, these findings indicate that alterations in circulating CA levels reflect the severity of the neurological insult and provide support for the use of CA measurements as a physiological marker of patient outcome in both the acute and chronic phases of traumatic brain injury.

A 58 year old woman with a history of hypothyroidism was evaluated for marked visual impairment and found to have the primary empty sella syndrome with multiple endocrine abnormalities. Visual field determination revealed preservation of vision only in the left inferior quadrants bilaterally. Failure of growth hormone (hGH), cortisol and prolactin to respond to insulin induced hypoglycaemia (0.1 U/kg), of luteinizing hormone (LH) and follicle stimulating hormone (FSH) to respond to gonadotrophin releasing hormone (GnRH, 100 microgram) and of thyrotrophin (TSH) and prolactin to increase after thyrotrophin releasing hormone (TRH, 500 microgram), confirmed the diagnosis of panhypopituitarism. Following water deprivation with a 9% loss in body weight, her urine osmolality remained at 204 mOsm./kg H2O), indicating that she had posterior pituitary deficiency as well. During surgical exploration, which was performed in an effort to improve her markedly impaired vision, a compromised vascular supply to the left optic nerve and chronic arachnoiditis was demonstrated. This case represents one extreme of functional impairment in a syndrome which is generally considered benign and which rarely requires therapeutic intervention. Our patient is compared to 29 reported cases of the primary empty sella syndrome with visual field defects. The operative findings in eight of these cases are reviewed. The need for a multidisciplinary approach and close follow-up of patients with an empty sella and functional deficits is emphasized. Surgical intervention including lysis of adhesions and chiasmapexy has been effective in selected cases in reversing or stabilizing visual field abnormalities.

WITHIN the past decade and particularly within the past 5 years, an unusual form of hyperthyroidism has received increasing attention (1–22). The hyperthyroid manifestations are generally self limiting, although some cases relapse, are accompanied by chronic inflammatory changes within the thyroid parenchyma, and are marked by a very low 131I uptake. Despite the usually abrupt onset of symptoms and the diffuse lymphocytic infiltration, thyroidal pain and/or tenderness is completely absent. Because this syndrome overlaps many of the features of both lymphocytic thyroiditis and subacute thyroiditis, there has been much debate about how to categorize it or whether to consider it a new disease entity. Nomenclature used by the several groups describing it includes: painless thyroiditis (7, 11, 17, 20), silent thyroiditis (3, 9, 19, 22), occult subacute thyroiditis (1), painless subacute thyroiditis (10, 14), subacute nonsuppurative thyroiditis (2), atypical (“silent”) subacute thyroiditis (16), lymphocytic thy...

Four women, aged 17 to 23, were evaluated for secondary amenorrhea of 12 to 36 months' duration. All were considered to have hypothalamic hypothyroidism on the basis of low thyroxine (T4) concentrations, inappropriately low thyrotropin (TSH) levels, with a normal TSH response to thyrotropin-releasing hormone (TRH, 500 microgram intravenously) in three, and absence of a pituitary lesion. Nevertheless, menses did not resume after adequate replacement with thyroid hormone. Investigation of the pituitary-gonadal axis revealed a normal increase in both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) following the intravenous administration of gonadotropin-releasing hormone (GnRH). Three subjects received clomiphene citrate, 100 mg/day for five days, but a normal menstrual cycle was not induced. It is concluded that the amenorrhea was not due to thyroid hormone deficiency but, like the hypothyroidism, to a hypothalamic abnormality involving secretion of the appropriate releasing hormone.

The mechanism of arginine (ARG) induced growth hormone (GH) and prolactin (PRL) release is poorly understood. Though dopamine (DA) is known to inhibit a number of GH and PRL secretagogues, it has been reported not to affect arginine mediated GH release. Our study was undertaken to study the interaction of DA and ARG further. Six healthy male volunteers received DA (4μg/kg/min) or saline from 0–240 min on two separate days. ARG (30 gms) was given 150–180 min on both days (Protocol I). In Protocol II 5 subjects received ARG on different days 30–60 min into a DA or saline infusion. On a third day only DA was given. Arginine alone was given in 2 separate infusions spaced 135 minutes apart to 5 volunteers (Protocol III). In Protocol I when ARG was given at 150 min, the maximal GH peak of 11.1 ± 1.3 ng/ml, which occurred 45 min later, was blunted by DA treatment (5.3 ± 1.1 ng/ml, p

The function of the pituitary-adrenal axis was studied in 23 acutely brain-injured, comatose patients (14 head trauma and 9 intracranial hemorrhage), who were treated with dexamethasone (16-64 mg/daily). Patients with normal intracranial pressure (ICP) and normal brain stem function (group 1) had decreased plasma cortisol levels (less than or equal to 5 micrograms/dl) within 36 h (mean +/- SEM, 2.4 +/- 0.3 microgram/dl; t 1/2, 18 h). In contrast, patients with elevated ICP (i.e. greater than 20 mm Hg; midline shift, or compressed ventricles) and normal brain stem function (group 2) had persistently elevated cortisol concentrations (15.4 +/- 2.6 micrograms/dl; P less than 0.001). Superimposition of brain stem dysfunction resulted in generally low cortisol levels regardless of the presence (group 4; 3.9 +/- 1.0 microgram/dl; P less than 0.001 compared to group 2) or absence (group 3; 2.1 +/- 0.5 microgram/dl) of elevated ICP. Plasma ACTH levels in 31 samples obtained before or during dexamethasone therapy in 14 patients irrespective of group were not elevated (45.6 +/- 12.5 pg/ml); there was no correlation between plasma ACTH and cortisol levels. Despite elevated cortisol values in group 2, ACTH levels were low (22.4 +/- 10.1 pg/ml). It is concluded that elevated ICP in the presence of normal brain stem function is a potent stimulus for adrenocortical activation which is not associated with elevated ACTH levels, and that the brain stem is involved in this response.

Acute illness is well known to affect thyroid function, but there are few studies correlating the severity of the underlying medical problem with indexes of thyroid function and little is known about its cause. Traumatically brain-injured patients were selected because they were a relatively homogeneous, previously healthy group with a condition whose severity was readily quantifiable. In 66 such patients, the relationships between changes in thyroid function tests (thyroxine, free thyroxine, triiodothyronine, reverse triiodothyronine, and thyrotropin levels), catecholamine and cortisol concentrations measured on admission and again four days after the accident, and neurologic function assessed by the Glasgow Coma Score (GCS) were studied. Triiodothyronine and thyroxine levels fell significantly within 24 hours of injury. Four days after the accident, patients with the greatest neurologic dysfunction had the lowest triiodothyronine and thyroxine levels; significant correlations were present between the Day 4 GCS and concomitant thyroxine (r = 0.47, p less than 0.0001), free thyroxine (r = 0.32, p less than 0.02), and triiodothyronine (r = 0.50, p less than 0.0001) levels. Reverse triiodothyronine values remained unchanged throughout the study even in the most severely affected patients; the rise in thyrotropin levels was not significant (1.2 +/- 0.2 to 1.7 +/- 0.3 microU/ml, p = NS). Patients who died or remained vegetative had thyroxine and triiodothyronine levels 30 percent to 50 percent lower than those who had a good recovery (p less than 0.05). Highly significant correlations were present between Day 4 thyroxine and triiodothyronine levels and admission and Day 4 norepinephrine and epinephrine concentrations. There was no association between admission or concomitant cortisol levels and thyroid function on Day 4; treatment with high-dose dexamethasone did not influence these indexes. Thus, patients with traumatic brain injury exhibit a gradient of thyroid dysfunction that occurs promptly, is dependent upon the degree of neurologic impairment, and reflects ultimate outcome. The significant association with catecholamine levels suggests a role for sympathetic nervous system activation in its causation, independent of a generalized stress response, since there is no correlation of thyroid test abnormality with the degree of adrenocortical secretion.

A follicle-stimulating hormone-producing pituitary tumor was demonstrated in a 28-yr-old eunuchoid-appearing male who presented with bilateral hemianopsia, oligospermia and an enlarged sella turcica. A basal luteinizing hormone of 16.0 mIU/ml (2nd IRP-HMG) was normal, but FSH was persistently elevated, 33.0–64.0 mIU/ml (normal < 0.8–16.0 2nd IRP-HMG). Provocative testing of hypophyseal function revealed absent growth hormone and deficient thyrotropin and corticotropin release, while prolactin increased normally following thyrotropin-releasing hormone (TRH) and decreased appropriately after l-dopa administration. Plasma testosterone was low. Immunofluorescent staining of the resected chromophobe adenoma using an anti FSH-antiserum revealed uniform fluorescence of the tumor cells. In vitro organ culture of three fragments of this pituitary adenoma demonstrated (mean ± sem) FSH and LH release of 311.7 ± 29.0 mIU/24 hr and 25.6 ± 2.0 mIU/24 hr respectively. No immunoassayable GH or TSH was demonstrab...

L-tryptophan (TP) availability has been shown to be a major factor regulating CNS serotonin concentration. Consequently, this essential amino acid was administered to healthy men and its effect on the pituitary hormone secretion investigated. The oral administration of 10 g of L-TP significantly increased L-TP levels by 15 min (19.1 ±2.0 to 55.2 ±.5 μg/ml, P < 0.01) and caused drowsiness in all subjects. In 11 men plasma cortisol decreased from a baseline of 8.1 ±0.9 /xg/dl to 5.6 ±.7 /μtg/dl by 45 min. The maximal nadir of 4.7 ±0.8 Atg/dl, a decrease of 43.2% (range 33-87%), occurred at 15-75 min and was followed by a rebound above baseline to 11.2 ±1.5 fig/dl. A significant inverse relationship existed during the first 45 min between TP and cortisol concentrations. TP treatment 15 min before the iv administration of regular insulin (0.1 U/kg) significantly blunted the peak corticotropin (ACTH) and cortisol response to hypoglycemia. The infusion of L-TP was followed by a significantly greater fall in ACT...

A pituitary tumor from a patient with severe Cushing's disease and marked hyperprolactinemia was extensively studied by immunohistochemical techniques. Tissues from two separate areas of the adenoma were found to contain similar cell proportions of PRL as well as ACTH and related peptides (beta-lipotropin, beta-endorphin, and alpha MSH). The tumor was composed of approximately 70% immunoreactive PRL cells and 5% ACTH-containing cells. Double immunostaining revealed that PRL or ACTH and related peptides were found in two distinct populations of tumor cells. These results document for the first time inappropriate synthesis and secretion of an unusual combination of pituitary hormones from a mixed pituitary adenoma.

Four women and one man with painless subacute thyroiditis presented with hypermetabolic signs and symptoms. Thyroxine (T4) and triiodothyronine (T3) resin uptakes (T3R) were increased but the 24 hour radioactive iodine (RAI) uptakes were less than 1 per cent. Surreptitious use of thyroid hormone was excluded. The thyroid was enlarged in one patient and nontender in all. Exophthalmos was absent. The protein-bound iodine level was 1.1 to 9.5 mug/dl greater than the T4 level. The sedimentation rate was normal or minimally increased, and antithyroglobulin and antimicrosomal antibodies were undetectable. In one hospitalized patient 84 per cent of the administered dose of 131I was recovered in the urine within 48 hours (normal 64 per cent) excluding extrathyroidal uptake. In all subjects the T4 and T3R levels fell to normal or slightly below normal within one to four months. An increase in the 2 and 24 hour RAI uptake to minimally increased or high normal values and return of the T4 and T3R levels to normal occurred in four of five patients within six months. In one of these, the administration of thyroid-stimulating hormone (TSH) resulted in an appropriate increase in 24 hour RAI uptake from 14.9 to 37.1 per cent. One woman remained clinically hypothyroid for six months with a low T4 concentration (3.2 mug/dl), an elevated TSH level (48 muU/ml) and evidence of a persistent organification defect -- two hour RAI uptake decreasing from 33 to 23 per cent after the administration of perchlorate and the 24 hour RAI uptake increasing from 32 to 76 per cent following the administration of TSH. At 21 months after the initial onset of her illness, she is euthyroid but increased RAI uptake persists. The clinical course in four of the five patients is similar to that in an additional eight patients treated during the same time period who presented with typical subacute thyroiditis. Thus, these patients have a form of painless subacute thyroiditis which presents as thyrotoxicosis but is differentiated from it by a low RAI uptake and in whom recovery of thyroidal iodine trapping is the first indicator of recovery. The hyperthyroidism is self-limiting and should be treated conservatively.

Plasma thyrotropin (TSH), thyroxine (T4), free T4, triiodothyronine (T3), growth hormone (GH), insulin (IRI), cortisol, glucose and osmolality were serially determined in a group of twelve patients admitted to a city hospital for accidental cold exposure with rectal temperature below 90 F. Plasma TSH and free T4 were constant. There was a significant decrease in plasma T4 and T3 which paralleled but was greater than the decrease in osmolality. Plasma cortisol increased over the first 7 hr of rewarming and then showed individual variation. Plasma GH and IRI concentrations were erratic and were independent of glucose concentration. Two of the three patients given 100 μg of synthetic thyrotropin releasing hormone (TRH) demonstrated a prompt rise in plasma TSH and T3. It is concluded that during hypothermia: 1) the hypothalamic-pituitary-thyroid axis is intact, 2) hypothermia is not a stimulus for TSH release in man, 3) neither GH or IRI nor their response to plasma glucose show a consistent change, 4) plasma...

The hypothalamic-pituitary axis was investigated in 11 adult patients with pituitary dysfunction: 8 with deficiency of all anterior hypophyseal hormones except prolactin and 3 with preservation of several hormones. The etiology of the hypopituitarism was diverse and included primary or metastatic intracranial neoplasms (4), head trauma (1), birth trauma (l), surgical stalk section (2) and idiopathic disease (3). Basal prolactin was elevated in 6 and normal in the remainder. Thyrotropin (TSH)-releasing hormone (TRH) administration increased plasma prolactin in all patients (mean ±sem, 201.1 ± 80.0%, p < 0.05) while TSH rose in 7 of 9 patients not taking thyroid hormone replacement. In contrast, chlorpromazine elicited a normal prolactin rise in only 1 of 8 subjects tested. In 9 patients oral l-dopa (500 mg) decreased prolactin 59.2 ± 7.5% (p < 0.01) by 90–240 min. Thus considerable pituitary function is demonstrable in many adult patients with hypopituitarism. Normal or elevated basal plasma prola...

A 17-year-old girl presented with euthyroid Graves' disease. Diplopia and extensive limitation of ocular motility bilaterally were the most remarkable features of this case. Even though the patient also had juvenile diabetes mellitus, treatment with systemic steroids was accomplished safely with complete recovery of ocular motility and the disappearance of diplopia in all fields of gaze.

At weekly intervals, five healthy volunteers received 100 μg of synthetic thyrotropin releasing hormone (TRH) 60 min into a four-hr infusion of each of the following agents: normal saline, isoproterenol, phentolamine, norepinephrine, and propranolol. Plasma thyrotropin (TSH) was determined serially in all five subjects, while in two plasma cortisol and growth hormone were also determined. Neither ∝ or β adrenergic stimulation nor blockade affected TRH induced TSH release and the mean maximal incremental rise of TSH during all infusions was not significantly different from the saline control. Plasma GH remained undetectable in both subjects in whom it was measured and plasma cortisol remained constant in one subject while in another a small but significant rise occurred after TRH, irrespective of infusion.

Previous studies have shown that the infusion of dopamine (DA; 4 µg/kg-min) both stimulates GH secretion and abolishes the GH response to hypoglycemia when insulin (0.1 U/kg) is given 30 min after the start of the infusion. Additional studies on the mechanism of this inhibitory effect are now reported. When insulin was given to seven normal male volunteers 15 min before the start of the DA infusion, the maximal GH increment (44.7 ± 5.7 ng/ml) was comparable to insulin alone (45.5 ± 5.3 ng/ml), and both were greater than the maximum increment when insulin was given 30 or 120 min into the DA infusion (17.3 ± 3.3 and 23.0 ± 7.4 ng/ml, respectively; P < 0.05). In contrast, DA potently inhibited PRL secretion regardless of the timing of DA and insulin; PRL fell during all DA plus insulin studies despite a maximal PRL increment after insulin alone of 24.4 ± 6.0 ng/ml. The GH response to 500 mg L-dopa given orally was inhibited by DA in a fashion similar to the insulin response. Thus, when L-dopa was given to si...

Five male patients with infertility due to biopsy-proven germinal cell aplasia were given a 100-microng bolus of luteinizing hormone (LH)/follicle-stimulating hormone (FSH)-releasing hormone (LRH), and the resultant LH, FSH, and testosterone responses were correlated with their histologic patterns on testicular biopsy. The basal and stimulated FSH values were elevated in four of five patients. Basal LH values were elevated in three patients, while two clearly had exaggerated LH and testosterone responses to LRH. Although there was little correlation between various parameters, elevated basal LH values were associated with Leydig cell hyperplasia. Higher basal FSH levels were present when fibrosis and complete aplasia of germinal elements were found in the same biopsy specimen, and the magnitude of the FSH response to LRH correlated positively with the basal concentration. The findings of elevated basal LH values, an exaggerated LH response to LRH, lack of testosterone response, and Leydig cell hyperplasia indicate a definite disturbance of the LH-testosterone axis in many patients with germinal cell aplasia. Therefore, the regulation of secretion of both gonadotropins appears to be abnormal in this disorder.5 infertile males with proven germinal cell aplasia received a 100 mcg bolus of LH FSH-releasing hormone (LRH), and the responses of LH, FSH, and testosterone were correlated with histologic patterns on testicular biopsy. 4 of 5 subjects had elevated basal and stimulated FSH values. 3 subjects had distinctly elevated basal LH levels, and 2 had markedly increased LH and testosterone responses to LRH. Basal LH values were associated with Leydig cell hyperplasia. The presence of fibrosis and complete aplasia of germinal elements in the same biopsy specimen was associated with higher basal FSH levels, with the magnitude of the FSH response correlating well with basal FSH concentrations. The results indicate a definite disturbance of the LH-testosterone axis in many patients with germinal cell aplasia.

A nephrectomized rat model was developed to examine PRL resistance to dopaminergic suppression, which is frequently present in humans with renal insufficiency. The MCR and the response of PRL to a dopamine (DA) infusion (0.4 microgram/kg . min) were measured in 24-h totally nephrectomized (TN) and sham-nephrectomized (SN) rats concurrently treated with alpha-methyl-p-tyrosine (AMPT), an inhibitor of DA synthesis. TN rats became significantly hyperprolactinemic within 1 day [36.2 +/- 7.1 vs. 18.5 +/- 2.5 (+/- SE) ng/ml; P less than 0.05]. SN and TN rats responded to AMPT with significant and sustained 3- and 5.5-fold increases in PRL, which DA reduced by 85% and 24%, respectively. Total nephrectomy decreased the PRL MCR by 58% (TN, 0.51 +/- 0.03; SN, 1.22 +/- 0.13 ml/min; P less than 0.001) and significantly increased the PRL secretion rate (TN, 79 +/- 10; SN, 37 +/- 8 ng/min; P less than 0.01). In the absence of DA infusion, AMPT reduced plasma DA to undetectable levels, while the median eminence DA contents in TN and SN rats were reduced to similar levels. Our data suggest that the totally nephrectomized rat is a suitable model to study PRL resistance to dopaminergic suppression, and that because DA does not cross the blood-brain barrier, the defect in uremia probably occurs at the level of the lactotroph.

The failure of adequate cortisol suppression after 1 mg dexamethasone in 50% of patients with endogenous depression has been attributed to abnormal hypothalamic-pituitary-adrenal axis regulation, resulting in high levels of adrenocorticotropic hormone (ACTH). Because studies of plasma ACTH have been conflicting, we studied plasma ACTH levels during the 24-hour dexamethasone suppression test in a homogeneous group of 29 hospitalized patients with primary endogenous depression and 19 normal volunteers. No differences were found in ACTH levels among normal volunteers, depressed cortisol suppressors, and depressed cortisol nonsuppressors at either 4 p.m. or 11 p.m.