Hypothalamic-pituitary Disorders Research Articles

Serum levels of insulin-like growth factor I in 152 patients with growth hormone deficiency, aged 19-82 years, in relation to those in healthy subjects.

Serum insulin-like growth factor I (IGF-I) levels within normal range for age have been reported to be common in adults with GH deficiency (GHD). Therefore, serum IGF-I levels were determined in 152 consecutive patients (71 women and 81 men) with evidence of hypothalamic-pituitary disorders or previous cranial radiation, who fulfilled the presently used criteria for GHD i.e. peak GH response below 3 microg/L at stimulation test. Patients treated for acromegaly were excluded. Forty-three patients, aged 19-63 yr, had childhood onset GHD, and 109, aged 23-82 yr, had adult-onset GHD. Their IGF-I levels were expressed in SD scores in relation to normal reference values based on 448 healthy subjects, aged 20-96 yr (247 women and 201 men). In healthy subjects a linear inverse correlation, without gender difference, was found between logarithmic transformed IGF-I levels and age (r = -0.774; P < 0.001). In contrast, no age dependency was found in GHD patients. All patients with childhood-onset GHD had IGF-I values below -2 SD, significantly lower than those in adult-onset GHD patients (-6.2 +/- 0.3 vs. -3.2 +/- 0.2 SD score; P < 0.001). In patients with adult-onset GHD, 34% of the IGF-I levels were within normal range, increasing to 40% in the subgroup above 60 yr of age, in whom 86% were diagnosed with hypothalamic-pituitary tumors. Normal IGF-I was more common in men than in women, but no difference was observed between patients with panhypopituitarism and those with partial pituitary insufficiency. High frequencies of IGF-I levels within the normal range were found in GHD patients with pituitary tumors (20 of 57 nonsecreting pituitary adenomas, 5 of 15 prolactinomas, 6 of 12 Cushing's disease, and 4 of 25 craniopharyngiomas), but in only 2 of 43 patients with GHD due to other causes. In conclusion, an IGF-I level below -2 SD seems to be of diagnostic value in GHD with onset in childhood or early adulthood, whereas values within normal range are common in patients over 60 yr of age, especially those with pituitary tumors. The outcome of GH replacement therapy may reveal whether the addition of IGF-I as a diagnostic criterion is of predictive value in older patients.

Nocturnal TSH Surge and TRH Test Response in the Evaluation of Thyroid Axis in Hypothalamic Pituitary Disorders in Childhood

We studied, by means of TSH nocturnal secretion and TRH test, 42 children (4.2–19.9 years) with hypothalamic pituitary disorders and 24 healthy euthyroid children (5.7–15.4 years) as control group. Patients were divided according to their serum values of FT₄ in group 1 (n = 27) with FT₄ ≥10.3 pmol/l and group 2 (n = 15) with FT₄ <10.3 pmol/l. TSH was measured by immunoradiometric assay. TSH nadir, TSH peak and TSH surge were calculated. Both groups differed significantly from control group in TSH surge values: group 1 (p < 0.05), group 2 (p < 0.01). TRH test was abnormal in 11/27 patients of group 1 and 10/15 patients of group 2. In group 1, 7 patients had normal tests, 2 had abnormalities in both tests, 9 had only TSH nocturnal surge altered and 9 showed only TRH alterations. All patients of group 2 presented thyroid axis abnormalities. In conclusion, in patients with hypothalamic pituitary disorders with low FT₄, no further investigation is required to demonstrate thyroid axis alterations, however in patients with normal FT₄, nocturnal TSH secretion and TRH test may be required to evidence thyroid abnormalities.

Defining the normal cortisol response to the short Synacthen test: implications for the investigation of hypothalamic‐pituitary disorders

To define the normal cortisol response to the Short Synacthen Test using four different cortisol immunoassays and to assess the implications for the investigation of hypothalamic-pituitary disorders. The cortisol response to 250 micrograms im ACTH1-24 (Synacthen, Ciba Geigy) in 100 healthy volunteers using four different cortisol immunoassays has been measured. In 44 newly diagnosed and untreated patients with pituitary disease, basal and 30 minute post-ACTH cortisol results were also determined using the four immunoassays. The distribution of cortisol results at all time points and for all methods were non-Gaussian and significant differences in the absolute values of the 5th-95th percentiles were found between methods (P < 0.01). At 30 min post-Synacthen in normals the 5th percentile of the cortisol response ranged from 510 to 626 nmol/l with the different methods. Similarly the relationship between assay results differed at different time points. No effect of age on the cortisol response was found but for stimulated cortisol values and the incremental responses females showed significantly higher responses than males (P < 0.05) for most methods. Although there was a significant positive linear correlation (P < 0.001) between stimulated and basal cortisol values for all methods, no significant relationship was found between the incremental response and basal cortisol values. In the pituitary disease patients basal and 30 minute post-ACTH cortisol results were significantly lower (P < 0.05 and < 0.001) than the control group using the same cortisol assay. When the results were compared to the 5th percentile of the gender and assay specific control group 33.3% of male and 17.4% of female patients failed the Synacthen test at 30 min. The definition of the 'normal' response to Synacthen should be both gender and method related at all time points. The data suggest that up to one-third of untreated patients with pituitary disease may have subtle defects in the hypothalamic-pituitary-adrenal axis.

To help patients with hypothalamic-pituitary disorders (patient's school)

There are many reasons for the pathological increase in prolactin levels in the blood (hyperprolactinemia). Even minimal stress, such as taking blood for research, can lead to a short-term increase in prolactin levels. Medications such as antiemetics (metoclopramide, raglan, cerucal), psychotropic (chlorpromazine), and birth control pills can increase hormone levels. If you have an elevated prolactin level in your blood test, be sure to tell your doctor about taking these drugs. Hyperprolactinemia can also be caused by thyroid insufficiency (hypothyroidism), which is easily detected by measuring the level of thyroid-stimulating hormone in the blood and is well compensated against the background of thyroid hormone replacement therapy (L-thyroxine). After the examination excludes the presence of a number of endocrine and non-endocrine diseases, a conclusion is drawn on the existence of an independent hypothalamic-pituitary pathology - hyperprolactinemic hypogonadism (GH).

Influence of insulin-induced hypoglycemia on the hemostatic and fibrinolytic system in patients with hypothalamicpituitary disorders

SummaryIn order to study the acute and prolonged effects of hypoglycemia on the hemostatic and fibrinolytic system we measured prothrombin fragment (F1+2), thrombin-antithrombin III complex (TAT), platelet factor 4 (PF4), β-thromboglobulin (âTG), factor VIII antigen (F VIII antigen), D-dimer, tissue-type plasminogen activator (t-PA) antigen, and plasminogen activator inhibitor (PAI-1) in 22 patients during insulin tolerance test. F1+2 and TAT increased significantly 15 and 90 minutes after administration of insulin, as did PF4 and âTG. At 4 and 24 hours, these parameters were not different from baseline. Factor VIII antigen was not significantly altered. D-dimer concentration did not change. However, the D-dimer/TAT ratio significantly decreased at 15 and 90 minutes but increased markedly above baseline at 4 and 24 hours. t-PA antigen was also found to be elevated at 15 and 90 minutes but had returned to baseline at 4 and 24 hours. PAI-1 concentration did not change. We conclude from these data that both coagulation and fibrinolysis are activated in the short-term response to acute insulin-induced hypoglycemia, followed by a prolonged activation of fibrinolysis. Our study may explain why patients undergoing insulin tolerance test, despite marked clotting and platelet activation, almost never develop thromboembolic complications.

To help patients with hypothalamic-pituitary disorders (patient's school) Itsenko-Cushing's disease

Itsenko-Cushing's disease (syndrome) is a disease associated with excessive blood levels of corticosteroids - hormones produced by small glands located above the kidneys and therefore called the adrenal glands. The main role in the changes occurring in the body with this disease is played by the hormone cortisol. These disorders can develop for a number of reasons, and therefore it is often necessary to conduct several tests to determine the cause of the disease.

To help patients with hypothalamic-pituitary disorders {patient’s school)

In the previous issue of the magazine, we talked about how the lack of pituitary hormones manifests itself and what modern methods of diagnosis and treatment of these conditions exist. Today we continue the story about the disease of the hypothalamic-pituitary system and dwell on the symptoms of excessive secretion of pituitary hormones.

Guidelines for patients with the hypothalamo-pituitary disorders; School for patients

In the previous issue, we talked about the structure and functions of the hypothalamic-pituitary system, as well as the need to create schools to help patients with hypothalamic-pituitary disorders. Today we want to focus on the manifestations of pituitary hormone deficiency and the basic principles of treatment of this pathology. Lack of pituitary hormones If the pituitary gland does not produce certain hormones or produces them in small quantities, then this condition is called hypopituitarism. Most often, this condition occurs due to the presence of a benign (i.e., non-cancerous) tumor of the pituitary gland or hypothalamus. If a person has a pituitary tumor, it can lead to a decrease in its functions by direct pressure of the tumor mass on the healthy part of the pituitary gland or as a result of surgical treatment or irradiation of the tumor. Less commonly, hypopituitarism is caused by infectious diseases of the brain (such as meningitis), significant blood loss (for example, during childbirth), head injuries, as well as rare diseases (sarcoidosis, etc.). I. Lack of ACTH. 1. What are the symptoms of ACTH deficiency? The most common symptom is fatigue, a feeling of general weakness, sometimes dizziness. Some patients have nausea and diarrhea.

General data on the hypothalamic-pituitary disorders (guidelines for patients)

Most diseases of the hypothalamus and pituitary gland are relatively rare, and therefore not only patients, but many doctors are new to their manifestations, diagnostic methods, treatment tactics, and most importantly, rehabilitation methods (including psychological). The low incidence of such diseases, however, does not detract from the importance of the problems faced by a particular patient. Currently, schools for teaching methods of self-monitoring of patients with diabetes mellitus and a number of other chronic diseases have been created and are actively functioning. There is a need to create such schools for patients with hypothalamic-pituitary diseases, since competent replacement therapy, which the vast majority of patients need after various interventions on the pituitary gland, significantly improves their quality of life. And if we take into account that the age of most patients does not exceed 40 years, then the importance of such schools, as well as the need to create a comprehensive rehabilitation system for these patients, become obvious. Schools for patients with hypothalamic-pituitary diseases have already been established and are successfully functioning in Western Europe, in particular in the UK. These schools help patients with Itsenko-Cushing's disease, prolactinomas, acromegaly, diabetes insipidus, pituitary dwarfism, panhypopituitarism. During classes, patients get acquainted with the anatomical and physiological features of the hypothalamic-pituitary system, its relationship with peripheral endocrine glands, they explain the main clinical manifestations of their disease, methods for its diagnosis and treatment. Patients are told about the meaning of certain terms used by attending physicians to describe their disease, as well as the possible side effects of the medications they take.

The development, reliability and validity of a disease specific quality of life model for adults with growth hormone deficiency.

Adults with GH deficiency frequently complain of lack of energy, fatigue, social isolation and problems with sexual relationships resulting in a low perceived quality of life. Previous studies of quality of life (QOL) in GH deficient adults have involved small numbers of patients and used measures not specifically designed for this patient population. We have devised a health related QOL model specifically designed for use in adults with GH deficiency and to assess the impact of future GH replacement therapy. Six measurements were chosen for inclusion in the model. Two were adapted for use after clinical interviews with 12 adult GH deficient patients: the Impact and the Life Fulfilment scales. The others were the Nottingham Health Profile, the Hospital Anxiety and Depression Scale, the Self-Esteem Scale and the Mental Fatigue Questionnaire. The reliability of the 6 measures was assessed by 2 methods: test re-test correlation and internal consistency (Cronbach's alpha). The validity of the Impact and Life Fulfilment scales was assessed by correlation with the other 4 scales. Questionnaires were completed by 32 adults with hypothalamic pituitary disorders and GH deficiency (11 male, mean age 35.1 years), with a stimulated maximum serum GH response less than 10 mU/l (mean 2.96). Two had previously received GH injections in childhood. The questionnaires were also completed by 32 age and sex matched control subjects. The 6 scales had test re-test correlations of 0.70-0.92 indicating reliability over time. The Impact and Life Fulfilment Scales and the Mental Fatigue Questionnaire had Cronbach's alpha scores of greater than 0.6 indicating their potential for use in clinical trials. The Impact and Life Fulfilment scales correlated significantly with many physical and psychological domains from the other 4 scales indicating these were valid in the assessment of health related QOL in GH deficient adults. Compared to the controls the patients with GH deficiency were significantly psychosocially disadvantaged in terms of depression, self-esteem, mental fatigue and life fulfilment. The results of the reliability and validity studies indicate that this health related quality of life model for use with adults with GH deficiency is a potentially valid and reliable tool that could be used to assess the effect of GH treatment.

Primary empty sella: differences and similarities between children and adults

To identify possible differences between empty sella in children and adults we studied 43 subjects (age 13.6 +/- 5.4 years, range 4.1-27 years) with hypothalamic-pituitary disorders and empty sella at magnetic resonance imaging. Pituitary function, presence of non-endocrine symptoms, perinatal history, sellar volume, pituitary height, midline or intrasellar anatomical abnormalities were evaluated. Twenty subjects had isolated growth hormone deficiency, 17 multiple pituitary hormone deficiency and 6 puberty disorders (3 precocious puberty, 2 idiopathic delayed puberty, 1 Kallmann syndrome). The group with multiple pituitary hormone deficiency had a higher percentage of subjects with complete empty sella, i.e. pituitary height < 2 mm (p = 0.016), or intrasellar anatomical abnormalities (p = 0.0002) than the other groups. The subjects with puberty disorders had a mean sellar volume higher than the other groups (p < 0.05). Apart from pituitary dysfunction, symptoms of the empty sella syndrome were infrequent (9.3% of cases) in our subjects. The age of our subjects, the frequent association between empty sella and pituitary dwarfism and the non-enlarged sellae suggest a different aetiology, perhaps congenital, for empty sella in our subjects. As in adults, empty sella may be associated with both pituitary hypo- and hyperfunction.

Empty sella in children and adolescents with possible hypothalamic-pituitary disorders.

Several computed tomographic scan studies have described empty sellae in children with hypothalamic-pituitary disorders. Magnetic resonance imaging, however, is a more precise technique for visualizing the intrasellar content, such as the stalk and pituitary lobes. Using magnetic resonance imaging, we studied 339 children and adolescents (mean age +/- SD, 12.7 +/- 4.5 yr) with possible hypothalamic-pituitary disorders to ascertain the frequency of primary empty sella and examine its relationships with other intrasellar abnormalities, pituitary function, and adverse perinatal events. One hundred and ninety-three patients had isolated GH deficiency, 43 had multiple pituitary hormone deficiency, 10 had diabetes insipidus, 17 had hypogonadotropic hypogonadism, 5 had idiopathic delayed puberty, 47 had precocious puberty, and 24 had other hypothalamic pituitary disorders of hyperfunction. One tenth (10.9%) of the patients (37 cases) had empty sella, with a marked variation of incidences among the disorders listed above. A statistically higher frequency of subjects with empty sellae was found only in patients with multiple pituitary hormone deficiency. Patients with and without empty sellae were not different in regard to age or sex. The incidence of empty sella in the various groups of patients was as follows: isolated GH deficiency, 8.8% (17 cases); multiple pituitary hormone deficiency, 34.9% (15 cases); hypogonadotropic hypogonadism, 5.9% (1 case); idiopathic delayed puberty, 40% (2 cases); and precocious puberty, 4.2% (2 cases). No patients with isolated diabetes insipidus or other hypothalamic-pituitary disorders had empty sellae. In the patients with empty sellae, abnormalities of the stalk or posterior lobe were found in 1 patient with isolated GH deficiency (5.9%), 13 patients with multiple pituitary hormone deficiency (86.7%), and no patients with puberty disorders. Likewise, adverse perinatal events were found only in 1 patient with isolated GH deficiency and 9 patients with multiple pituitary hormone deficiency. These findings suggest that empty sella is not rare in children and adolescents evaluated for hypothalamic-pituitary disorders, particularly if there is multiple pituitary hormone deficiency. Empty sella can be found regardless of abnormalities of the stalk and posterior lobe, and adverse perinatal events do not seem to be the primary etiological factor. Empty sella is usually associated with pituitary hypofunction, but it can be found in patients with hyperfunction of the hypothalamic-pituitary-gonadal axis.

Pulsatile Gonadotropin- Releasing Hormone Therapy for Ovulatory Disorders

Pulsatile GnRH remains a physiologic method of inducing ovulation that is effective and safer than other parenteral preparations. Its lower rate of acceptance in the United States stands in curious contrast to its widespread usage in other countries as a second-line (postclomiphene) technique of choice for ovulation induction. In a high-technology era such as ours, women who may benefit from pulsatile GnRH therapy should not be forgotten. By far the most favorable results are obtained in women with primary or secondary hypothalamic amenorrhea. In such women, pregnancy rates appear comparable to those achieved with exogenous gonadotropins with a much lower risk of multiple pregnancy and ovarian hyperstimulation. These positive aspects, combined with the decreased need for clinical monitoring and the increased sense of control imparted to the patient, lead to the conclusion that women with uncomplicated hypothalamic-pituitary disorders are the ideal patient group to consider for therapy. The application of pulsatile GnRH therapy to other groups of women relies on limited data. By all means, women with polycystic ovarian syndrome who have not ovulated or conceived after other forms of treatment should be considered because reasonable pregnancy salvage can be obtained. We have noted a first-cycle successful pregnancy after failure of exogenous gonadotropins, with or without a superimposed GnRH agonist, and even in vitro fertilization with multiple embryo transfers. Before such invasive, high-technology procedures are entertained, it would appear prudent to consider this simple alternative in women with an overactive hypothalamic-pituitary axis, as seen in polycystic ovarian syndrome. Other ovulatory defects also may be amenable to treatment with pulsatile GnRH, but their practical usefulness will await further clinical study.

Hypothyroidism and Deficiency of the Nocturnal Thyrotropin Surge in Children with Hypothalamic Pituitary Disorders*

The circadian pattern of serum TSH in normal children, aged 5-18 yr, is characterized by a nocturnal surge and is presumably related in some way to a biological clock within the central nervous system. To look for patients deficient in the nocturnal TSH surge, we studied 52 children with hypothalamic-pituitary disorders. Thirteen of the children were hypothyroid, as judged by subnormal serum free T4 (FT4). The hypothyroid patients had a mean nocturnal TSH surge of 22% (range, -30% to +114%), significantly less than that of normal controls (mean, 124%; 95% confidence limits, 47-300%; n = 96; P less than 0.01). Only 1 of the hypothyroid children had a value for the nocturnal TSH surge (114%) that was within the normal range. Nineteen of the 52 patients with hypothalamic-pituitary disorders had subnormal nocturnal TSH surges; their mean iodothyronine values were significantly less than those of the 33 patients with normal surges [total T4, 73 +/- 4 (mean +/- SE) vs. 109 +/- 3 nmol/L (P less than 0.01); FT4, 13 +/- 1.0 vs. 19 +/- 0.5 pmol/L (P less than 0.01)]. These data demonstrate a clear association of a deficient nocturnal TSH surge and low iodothyronine concentration in children with hypothalamic-pituitary disorders. We performed both TRH tests and nocturnal TSH surge tests in 11 of the children with central hypothyroidism; TRH was abnormal in only 2, while the nocturnal surge test was abnormal in 10 of the 11. We suggest that the nocturnal surge of TSH is important for maintenance of thyroid function and conclude that the nocturnal TSH surge is a much more sensitive test than the TSH response to TRH for the diagnosis of central hypothyroidism.

Growth and pubertal development in children with congenital and acquired hypothalamic-pituitary abnormalities

Hypothalamic-pituitary disorders, either congenital or acquired, frequently affect the growth and pubertal development of children. Two distinct groups were investigated. The first group consisted of 70 patients with congenital optic nerve hypoplasia (ONH): 16 (73%) of the 22 patients had growth hormone deficiency; among the 21 patients who were old enough and had adequate data for pubertal evaluation, 2 (10%) had delayed or absent puberty and 4 (19%) had precocious puberty. In the second group, 14 children had undergone head irradiation and/or surgery for brain/orbital tumors. Of these, 21% had precocious puberty, 36% had delayed puberty, and 10 (90%) of 11 patients tested had growth hormone deficiency. The pubertal growth spurt can conceal hGH deficiency. Linear growth continues at a rate near normal for childhood but low for puberty. Careful monitoring of growth and early initiation of growth hormone replacement are essential to achieve a normal adult height in adolescents with hypothalamic-pituitary disease.

Evidence for altered opioid activity in patients with cancer

Endogenous opioid peptides have been shown to be involved in the regulation of tumour growth. At present, however, no data are available about the secretion of opioid peptides in cancer patients. To draw some preliminary conclusions on opioid brain function in human neoplasms, we evaluated hypophyseal hormone responses to the administration of a met-enkephalin analogue, FK 33-824. The study included 14 patients affected by early or advanced neoplastic disease, 12 healthy subjects and 7 patients with a chronic medical illness other than cancer. FK 33-824 was given intravenously at a dose of 0.3 mg. Venous blood samples were collected at zero time, and 30, 60 and 120 min after drug administration. In each sample, PRL, GH, LH, cortisol and beta-endorphin levels were measured by RIA. In all normal subjects and in patients with non-neoplastic chronic illness, FK 33-824 induced a rise in PRL and GH levels, and a decrease in LH, cortisol and beta-endorphin. A normal endocrine response to FK 33-824 was seen in our cancer patient only, while in the other cases with tumour no hormonal changes or a paradoxical response were seen after FK 33-824. Based on the fact that an abnormal endocrine response to FK 33-824 has been described in hypothalamic-pituitary disorders, in which anomalous brain opioid activity has been demonstrated, these results suggest the existence of an altered function of the opioid system in cancer patients, the clinical importance of which remains to be determined.

Assays for follicle stimulating hormone and luteinising hormone: guidelines for the provision of a clinical biochemistry service.

The measurement of serum follicle stimulating hormone (FSH) and luteinising hormone (LH), together with the appropriate sex steroid, is of great value in the investigation of delayed and precocious puberty, hypogonadism, subfertility, polycystic ovarian disease and hypothalamic-pituitary disorders. Dynamic function testing of the hypothalamic-pituitary-gonadal axis should be restricted to a few defined situations. Sequential LH measurements, either in serum or in urine, may be used to time ovulation during artificial insemination or in vitro fertilisation programmes. No special precautions are necessary when sampling for FSH and LH measurement; serum is preferred to plasma and should be stored frozen before assay. Aliquots of timed urine specimens of known volume should be stored frozen without preservative. Gonadotrophin results should be available within 2-3 weeks; laboratories unable to meet this schedule are advised to send their samples to a Regional Centre for assay. Reagents for the radioimmunoassay of FSH and LH are readily available, and standard techniques have been developed for their use. Laboratories using 'in-house' methods should pay particular attention to the matrix used for preparing standard solutions, the purification of radioligands and the optimisation of the separation system. Low cost matched reagents of proven performance are available in kit form from the Chelsea Hospital for Women; several commercial kits are also available, although few are widely used in the UK. The overall performance of laboratories in the UK External Quality Assessment Scheme (EQAS) for FSH and LH has remained steady for several years. Of the 130 participants, only about 15% in each scheme have 'good' performance (cumulative bias less than 10%, plus cumulative variability of bias less than 10%), whilst a similar proportion have 'unacceptable' performance (cumulative bias greater than 20% and/or cumulative variability of bias greater than 25%). The remaining 70% of laboratories have 'adequate' performance but are at risk of producing results that are clinically misleading. Within any one method group, the performance of FSH and LH assays are closely related. Optimal assay performance depends upon sensible laboratory management to ensure skilled operators, a regular programme of reagent/kit renewal, comprehensive internal and external quality assessment, and attention to detail in all aspects of gonadotrophin assay. The working range of each individual assay should be defined and no absolute result reported from outside this range.(ABSTRACT TRUNCATED AT 400 WORDS)

PULSATILE PROLACTIN SECRETION IN HYPOTHALAMIC-PITUITARY DISORDERS

We have studied nine children with a variety of hypothalamic pituitary disorders and delayed puberty, before and during nocturnal pulsatile GnRH therapy given subcutaneously in a dose of 2 - 4 ug every 90-120 minutes. Initial age ranged from 13.5 - 18 years. The duration of therapy was >0.5 years. Overnight serum profiles of prolactin, growth hormone and gonadotrophins were obtained by blood sampling at 15 minute intervals.In the three severely growth hormone deficient patients there were very low levels of prolactin (0-150 mIU/L), without appreciable pulsatility or sleep-related rise. In the remainder there was no clear relationship between prolactin levels and GnRH or gonadotrophin pulses. In those patients with normal growth hormone secretion, including two with isolated gonadotrophin deficiency, there was a temporal relationship between growth hormone and prolactin pulses.These results therefore seem to contrast with data from adult studies, in that pulsatile prolactin secretion was more related to growth hormone status and release than to GnRH or gonadotrophins. This may have important implications for our understanding and management of hypothalamic-pituitary disorders.

Growth hormone release in response to human pancreatic tumor growth hormone-releasing hormone-40 in children with short stature.

Forty children with short stature were evaluated for GH reserve after pharmacological tests and after a single iv injection of human pancreatic tumor GH-releasing hormone [hpGRH-40). These children were grouped into four diagnostic categories: 1) idiopathic GH deficiency (n = 10); 2) organic hypopituitarism (n = 7); 3) intrauterine growth retardation (n = 5); and 4) constitutional delay of growth and/or familial short stature (n = 18), by standard clinical criteria and physiological and pharmacological tests of GH reserve. Venous blood was sampled for GH concentrations on 2 consecutive days: on day 1, after the iv administration of L-arginine (0.5 g/kg for 30 min) and oral administration of L-dopa (9 mg/kg), and on day 2, after the administration of hpGRH-40, 3.3 micrograms/kg, as an iv bolus. No GH-deficient patient in categories 1 or 2 increased his/her circulating GH concentration to more than 7 ng/ml after the arginine-L-dopa test; however, six children had marked GH responses after hpGRH-40 administration. As a group the lowest peak responses (mean +/- SE) to GRH were found in the organic hypopituitary (3.4 +/- 1.1 ng/ml) and in the idiopathic GH deficiency (8.2 +/- 2.4 ng/ml) categories. All children in the intrauterine growth retardation and constitutional delay of growth (controls for the GH-deficient children) responded briskly to hpGRH-40, although there was wide variation of the peak GH levels (5-51 ng/ml). Circulating concentrations of somatomedin-C did not differ in subjects in any category 24 h after hpGRH-40 injection when compared to basal values. These data indicate that hpGRH-40 can be employed to evaluate GH reseve in short children and may be useful in the diagnosis of hypothalamic-pituitary disorders.

Part 2. Response of Corticotropin to Insulin-induced Hypoglycemia and Metyrapone in Patients with Hypothalamic-Pituitary Disorders

Pediatrics InternationalVolume 23, Issue 2 p. 264-265 Part 2. Response of Corticotropin to Insulin-induced Hypoglycemia and Metyrapone in Patients with Hypothalamic-Pituitary Disorders First published: November 1981 https://doi.org/10.1111/j.1442-200X.1981.tb00458.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume23, Issue2November 1981Pages 264-265 RelatedInformation