Increased prolactin secretion and thyrotrophin response to thyrotrophin releasing hormone in Klinefelter's syndrome

Summary.  The reports published thus far on prolactin and thyrotrophin secretion in patients with Klinefelter's syndrome are controversial. The aim of the present study was to investigate the interrelation between prolactin on one hand, and hormones of the hypothalamic-pituitary-gonadal axis and thyrotrophin, on the other, in males with Klinefelter's syndrome. Fifteen patients with Klinefelter's syndrome, aged between 17 and 43 years, and 15 healthy males, aged 22–35 years, were studied. Mean ± SD basal serum prolactin levels were 529.6±174.6 mU l^-1 in the patients, and 270.1±113.0 mU l^-1 in the control group ( P <0.001). Following 200 μg thyrotrophin releasing hormone, an enhanced prolactin response was seen in the males with Klinefelter's syndrome. There was no evidence of any of the well-known causes of hyperprolactinaemia. The response of thyrotrophin to thyrotrophin releasing hormone was more pronounced in Klinefelter patients in comparison with controls. Presumably, in Klinefelter's syndrome both alterations—of prolactin and thyrotrophin secretion—may be caused by decrease of testosterone levels or they could reflect a disturbance in neuroendocrine regulation with some neurotransmitter imbalance.     

Gonadal dysfunction after testicular torsion: luteinizing hormone and follicle-stimulating hormone response to gonadotropin releasing hormone

We studied 14 postpubertal patients at an average of 33 months after treatment for testicular torsion. Of these patients 11 had been treated by detorsion and 3 by orchiectomy. Five normal male volunteers of the approximate age of the study group served as controls. The patients treated by detorsion were subdivided into 3 groups based on the degree of atrophy of the detorsed testicle: group 1--no testicular atrophy (5), group 2--25 per cent testicular atrophy (2) and group 3--greater than 90 per cent testicular atrophy (4). Mean duration of torsion was greatest in the orchiectomy group (161 hours) compared to 6, 16 and 29 hours for groups 1, 2 and 3, respectively. The serum luteinizing hormone and follicle-stimulating hormone response to an intravenous bolus of 100 mcg. synthetic gonadotropin releasing hormone was measured in all patients. All groups had a greater mean follicle-stimulating hormone response to gonadotropin releasing hormone stimulation than controls (p less than 0.05). Patients who underwent orchiectomy had the greatest follicle-stimulating hormone response to gonadotropin releasing hormone stimulation. Mean luteinizing hormone response to gonadotropin releasing hormone stimulation was normal in patients without atrophy (group 1) but it was greater than controls in patients who had atrophy (groups 2 and 3) or who underwent orchiectomy (p less than 0.05). Several conclusions could be made from our study. All patient groups treated for torsion had evidence of testicular dysfunction. Patients who underwent orchiectomy displayed more testicular dysfunction than patients who had atrophy after detorsion. Testicular dysfunction after torsion is more likely to involve spermatogenic before Leydig cell function.     

Thyroid function and endocrine abnormalities in elderly patients with severe chronic obstructive lung disease.

Serum pituitary and thyroid hormones, testosterone, and the response of pituitary hormones to thyrotrophin releasing hormone were measured in 20 inpatients (mean age 68, range 42-81 years) with severe chronic obstructive lung disease and in 15 control convalescent inpatients (mean age 73, range 57-83 years) who had normal respiratory function. No significant differences were found in total and free thyroid hormone concentrations and basal concentrations of thyrotrophin, growth hormone, and prolactin; and their increments after injection of thyrotrophin releasing hormone were similar in patients with chronic obstructive lung disease, and control patients. Three patients with chronic obstructive lung disease, however, had no thyrotrophin responses to thyrotrophin releasing hormone. In men, low testosterone concentrations were found both in patients with chronic obstructive lung disease and in controls. Luteinising hormone concentrations were higher in men with chronic obstructive lung disease (p less than 0.02), whereas concentrations of follicle stimulating hormone in the two groups were not significantly different. There was no significant correlation between arterial blood gas tensions and these hormone measurements. General effects of age and illness may be more important than direct effects of hypoxia in determining hypothalamic-pituitary function in elderly patients with chronic obstructive lung disease.     

Hypothalamic-pituitary dysfunction in respiratory hypoxia.

Eight hypoxic male patients with stable chronic obstructive airways disease were submitted for combined anterior pituitary function testing. All subjects showed normal growth hormone and essentially normal cortisol responses to adequate hypoglycaemia, two subjects showed delayed responses of thyroid stimulating hormone to administered thyrotrophin releasing hormone and all had basal prolactin levels within normal limits. Basal levels of luteinising hormone were significantly lower than in the group of age-matched controls (p less than 0.02) but there was a normal increment after the injection of gonadotrophin releasing hormone. Basal levels of follicle stimulating hormone were significantly lower than in the controls (p less than 0.01), and there was also a reduced response from the pituitary after injection of gonadotrophin releasing hormone (p less than 0.01). Resting levels of the thyroid hormones thyroxine and tri-iodothyronine were normal while the expected subnormal testosterone level was observed (p less than 0.05). These results show that hypoxia can produce abnormalities of hypothalamic-pituitary function and that these are primarily located in the hypothalamic-pituitary-testicular axis.     

Hidradenitis suppurativa: evidence for an endocrine abnormality

Women patients with premenstrual exacerbation of hidradenitis suppurativa have been studied to determine if an endocrine abnormality can be detected. A functional disorder of the hypothalamopituitary axis was found in 13 patients with hidradenitis when compared with 9 controls. In response to a combined thyrotrophin releasing hormone and gonadotrophin releasing hormone test, the prolactin and TSH responses were significantly greater in the hidradenitis patients than the controls. No significant differences were found in the mean basal levels of oestrogen, progesterone, testosterone, dehydroepiandrosterone sulphate, T3 and T4. These results may reflect a disturbance of feedback signals from peripheral hormones, rather than a primary dysfunction of the control of specific anterior pituitary cells.     

Growth hormone releasing hormone test for infertile men with spermatogenetic maturation arrest

PURPOSE: Growth hormone has an important role in the function of the male reproductive system. We investigated infertile men with impaired growth hormone secretion. MATERIALS AND METHODS: Growth hormone status was studied in 8 fertile men and 9 infertile men with azoospermia due to spermatogenetic maturation arrest. Growth hormone releasing hormone, the specific stimulatory neurohormone, was used in the growth hormone stimulation test. A dose of 100 microg. of growth hormone releasing hormone was infused intravenously and serum growth hormone concentrations were measured at 0, 15, 30, 60, 90 and 120 minutes. Serum follicle-stimulating hormone, luteinizing hormone, prolactin, testosterone and estradiol were also measured before the test. RESULTS: Serum follicle-stimulating hormone concentrations were significantly increased in the azoospermic group and basal levels of growth hormone were similar to those in the control group. Serum growth hormone concentrations increased after injection of growth hormone releasing hormone and the levels of growth hormone peaked after 30 minutes in both groups. At time 30 minutes growth hormone levels had decreased significantly more in the azoospermic group than in the controls. Men with azoospermia due to spermatogenetic maturation arrest had a low response to the growth hormone releasing hormone test. CONCLUSIONS: Relative growth hormone insufficiency, which may be caused by reduced reactivity to growth hormone releasing hormone in pituitary growth hormone secretory cells, is strongly related to spermatogenic dysfunction.     

Growth hormone response to acute growth hormone releasing hormone administration in uraemic patients on haemodialysis.

To examine the response of growth hormone (GH) to growth hormone releasing factor (GHRF) in patients on haemodialysis, we performed the acute GHRF test (50 micrograms administered intravenously as a bolus) in 10 uraemic male patients on haemodialysis and eight normal controls. Each patient was tested before and after a haemodialysis session (at 08.30 and 12.30). Controls were tested on the same time schedule. At 08.30, patients had significantly greater basal and peak GH values (2.5 +/- 0.6 and 27.8 +/- 5.5 micrograms/l) than controls (0.68 +/- and 11.5 +/- 4 micrograms/l). After the haemodialysis session, basal and peak values declined significantly (P less than 0.01) in the uraemic group (0.5 +/- 0.03 and 3.1 +/- 1.1 micrograms/l), whereas the controls did not show such a change in the 12.30 test. Basal and intratest glycaemic values were comparable both before and after haemodialysis. After dialysis test results did not change either with the use of glucose-free dialysate or with bicarbonate buffer. Uraemic patients display a greater GH response to GHRF injection than normal subjects, and this response decreases after haemodialysis. The degree of reduction has no relationship with either glycaemia or the dialysate buffer. We suggest that other GH secretion regulating factors are altered by the haemodialysis procedure.     

Cyclical mastalgia and breast pathology

Histologic examination of mammary tissue from 39 patients with cyclical mastalgia and 68 with no mastalgia disclosed that fibrocystic disease was not in itself the cause of the cyclical condition. Nor did the study support the traditional concept of a relationship between major dysfunction of the internal genital organs and cyclical mastalgia. Although the organic basis for cyclical mastalgia is unknown, several observations strongly suggest that it is located in the mammary stroma. Future investigations of the organic basis for cyclical mastalgia should include the mammary stroma.     

Pituitary Gonadal Function in Diabetic Male Patients with and without Impotence

Assessment of pituitary function was undertaken in diabetic male patients with and without impotence, and in normal subjects, using a combined gonadotropin releasing hormone (GnRH) and thyrotropin releasing hormone (TRH) test. Basal plasma levels of testosterone, gonadotropins, PRL and TSH were similar in the diabetic patients and controls. Following the administration of I.V. GnRH 150 microgram and TRH 500 microgram, diabetic patients with impotence demonstrated a lower LH response at 30 and 150 minutes and an increased PRL response at 20 minutes, which was statistically significant when compared to controls. FSH and TSH were similar in the diabetic patients and controls. The GnRH and TRH test was repeated in impotent diabetic patients while receiving 0.8-1 mU/kg/hr of insulin through an infusion pump. No difference in LH and PRL response could be demonstrated. These results demonstrate that following GnRH and TRH test, diabetic patients with impotence have a significantly different LH and PRL response than controls. In these patients acute control of hyperglycemia using an insulin infusion pump did not reverse the abnormal response.     

DES lead-in to use of luteinizing hormone releasing hormone analogs in treatment of metastatic carcinoma of prostate

Luteinizing hormone releasing hormone (LHRH) analogs have been shown to be an effective alternative endocrine treatment of metastatic prostatic carcinoma. After a transient stimulation of testosterone (T) and dihydrotestosterone (DHT) during the first week of therapy, continued administration of LHRH analogs has reliably suppressed serum androgens to castrate levels. About 10 per cent of previously untreated patients begun on LHRH therapy will experience transient worsening of disease symptoms corresponding to the initial rise in androgen levels. In an attempt to eliminate the early rise of T and DHT, 9 patients with metastatic prostatic carcinoma were pretreated with diethylstilbestrol (DES), 3 mg/day, for one week prior to the initiation of LHRH therapy. Following this, both DES and LHRH were given concomitantly for a week, after which DES was discontinued. LHRH was then continued as long as patients experienced clinical benefit. T and DHT levels were performed pre-study and on days 4, 8-11, 13, 15, and 29 of study. Results indicate that pretreatment with DES did not completely prevent the rise in T and DHT seen during the first week of LHRH therapy, although T and DHT levels rose to only slightly above baseline during the first four days. T and DHT levels then markedly decreased, and castrate levels were achieved by day 29 of treatment.     

Determining dosing intervals for luteinizing hormone releasing hormone agonists based on serum testosterone levels: a prospective study

PURPOSE: Long acting luteinizing hormone releasing hormone agonists are the predominant form of androgen suppression in the treatment of prostate cancer with the goal of maintaining castrate levels of testosterone. Current dosing of luteinizing hormone releasing hormone agonists does not include monitoring the end organ response of serum testosterone. Recent evidence suggests standard dosing regimens fail to achieve castrate levels of testosterone in some patients while in other patients testosterone can remain at castrate levels longer than the manufacturer recommended dosing interval. We prospectively evaluated patients with prostate cancer receiving luteinizing hormone releasing hormone agonist hormonal therapy to determine the length of time that serum testosterone remains at or below castrate levels. MATERIALS AND METHODS: A 3-month dose of 22.5 mg leuprolide was administered to all patients as a first dose followed by a second dose 3 months later. Serum testosterone and prostate specific antigen were measured prospectively before starting hormonal therapy, after the first dose (12 weeks) and again following the second dose (24 weeks) to assess if castrate levels of testosterone (50 ng/dl or less) had been reached. At 24 weeks if patient serum testosterone was 50 ng/dl or less, then 22.5 mg leuprolide were not administered, and serum testosterone and prostate specific antigen were checked monthly. When serum testosterone was greater than 50 ng/dl a subsequent dose of 22.5 mg leuprolide was given. Serum testosterone and prostate specific antigen were then checked 3 months later and monthly thereafter until testosterone was greater than 50 ng/dl. Thus, the time that testosterone remained at castrate levels could be accurately established. RESULTS: From February 2003 to August 2005, 42 patients were treated in this manner with a median followup of 18 months (range 10 to 30). Average patient age was 77 years. Median Gleason grade was 7 (range 6 to 9). Median pretreatment prostate specific antigen was 15.1 ng/ml (range 0.6 to 433) and median posttreatment prostate specific antigen was 0.74 (less than 0.1 to 120). The median dosing interval was 6 months (range 5 to 12). Three patients had an increase in prostate specific antigen while receiving treatment despite castrate levels of testosterone. No patient required more frequent dosing than every 5 months. CONCLUSIONS: Testosterone based luteinizing hormone releasing hormone agonist therapy makes empirical sense. It represents continuous androgen ablation based on the patient physiological end point, namely testosterone. Early data suggest that using serum testosterone to guide luteinizing hormone releasing hormone dosing is safe, efficacious and cost-effective. By following end organ response, patients receive individualized care and more accurate androgen suppression therapy.     

Cyclical mastalgia: clinical and mammographic observations in a screened population

The incidence of cyclical mastalgia in well women presenting for breast screening was 69 per cent. The incidence of cyclical mastalgia increases with age up to the menopause. There was a higher incidence of 'high risk' mammographic patterns and a lower incidence of 'low risk' patterns, according to the Wolfe classification, in women with cyclical mastalgia compared with the rest of the screened population. This finding correlated with the severity, duration and need for treatment. The differences in breast pattern did not persist after the menopause. The question of whether or not cyclical mastalgia can be regarded as a risk factor for breast cancer is uncertain and needs further evaluation.     

A double-blind randomized controlled trial of toremifen therapy for mastalgia

HYPOTHESIS: Toremifen is effective in reducing breast pain and does not increase the incidence of adverse events as a therapy for moderate to severe mastalgia.Design and PATIENTS: In a double-blind randomized controlled trial, patients with moderate to severe mastalgia received toremifen citrate, 30 mg daily, or a placebo tablet for 3 menstrual cycles and were followed up for breast pain score and adverse events. The serum levels of estradiol, progesterone, and prolactin were examined before treatment and correlated with the response rate to toremifen treatment. RESULTS: Seventy-two (69.2%) of 104 patients receiving toremifen and 29 (31.9%) of 91 receiving placebo responded to the treatment, with reduction in breast pain score of more than 50% (P<.001). Among the patients with cyclical mastalgia, the response rate for toremifen was 76.7% (59/77), whereas the response rate for placebo was 34.8% (23/66; P<.001). In contrast, the response rate of patients with noncyclical mastalgia was 48.1% (13/27) for toremifen and 24.0% (6/25) for placebo (P = .09). Adverse events were observed in 44 (42.9%) of 104 patients receiving placebo and 46 (50.5%) of 91 patients receiving toremifen (P = .45). A positive correlation between baseline breast pain score and serum estradiol level was observed in patients with cyclical mastalgia (r = 0.35, P = .003). CONCLUSIONS: Toremifen effectively relieves moderate and severe cyclical mastalgia and tends to exert a positive therapeutic effect on noncyclical mastalgia. In addition, toremifen therapy does not increase the incidence of intolerable adverse event. Therefore, it is a feasible therapy for mastalgia, especially cyclical mastalgia.     

Changes of pituitary hormones in brain death

Summary In six patients with clinical and electroencephalographic signs of brain death, pituitary hormones such as prolactin, human growth hormone (GH), luteinizing hormone (LH), and thyrotrophin (TSH) were measured in blood close to the demonstration of intracranial circulatory arrest by angiography. In addition, pituitary hormone releasing tests and an insulin test were carried out in two patients. The results showed that no patient had a general decrease in hormone levels, according to their biological half life times, which suggests there still was some function in the hypothalamus and pituitary. This was supported by the results of the stimulation tests. It is concluded that in brain death some basal parts of the brain may still be perfused despite the fact that angiography indicates circulatory arrest in these areas.     

Assessment of thyroid function with hormone assays

Measurement of serum thyroid hormone and TSH levels provide diagnostic information in the majority of patients with thyroid dysfunction. The test strategy in hyperthyroidism differs from that in hypothyroidism. Serum T4 is a good test for hyperthyroidism in patients with normal thyroid hormone-binding protein levels. When binding proteins are abnormal serum free T4 is a much more accurate test for hyperthyroidism than serum T4. Serum T3 and the TSH response to TRH are useful tests for the early diagnosis of hyperthyroidism. Serum TSH is a very sensitive indicator of primary hypothyroidism rising already at the subclinical stage of the disease. Serum T4 and free T4, but not serum T3, are useful for the verification of clinical hypothyroidism. Determination of the TRH-stimulated TSH level is important for the differential diagnosis of pituitary and hypothalamic hypothyroidism. It is imperative to recognize that thyroid tests are often abnormal in various non-thyroidal diseases and that administration of drugs can affect these tests. Serum rT3 is of some value for the assessment of thyroid function in patients with non-thyroidal disease.     

Management of cyclical mastalgia in oriental women: pioneer experience of using gamolenic acid (Efamast) in Asia.

BACKGROUND: In most Western countries gamolenic acid is the first-line treatment for women with cyclical mastalgia. METHODS: A prospective study was carried out in the breast referral clinic of the Department of Surgery, University of Hong Kong to evaluate the treatment of cyclical mastalgia using gamolenic acid provided in evening primrose oil (Efamast, Scotia Pharmaceuticals Ltd, Scotia House, Stirling, Scotland) as a pioneer experience in Asia. In addition, the features of cyclical mastalgia in Oriental women were studied by conducting a survey using anonymous questionnaires. RESULTS: Sixty-six women with disturbing cyclical mastalgia seen by one breast surgeon were followed up with a breast pain diary. Thirty-four women had persistently disturbing mastalgia and were commenced on Efamast. Responses were measured at 3 and 6 months according to a standardized protocol. An overall useful response rate of 97% was observed at 6 months. Side-effects were found in 12% but all were insignificant. CONCLUSIONS: Efamast may be recommended as a first-line specific treatment for Oriental women with disturbing cyclical mastalgia.     

An implant releasing the gonadotropin hormone-releasing hormone agonist histrelin maintains medical castration for up to 30 months in metastatic prostate cancer

PURPOSE: The administration of gonadotropin hormone-releasing hormone agonists is well established for treating metastatic prostate cancer. In an ongoing study we evaluated the effect of a long acting implant that releases the gonadotropin hormone-releasing hormone agonist histrelin ([ImBzl]D-His6,Pro9-Net) in 15 patients with disseminated prostate cancer. MATERIALS AND METHODS: The 2.6 cm. implant releasing 60 microg. histrelin daily is inserted subcutaneously into the upper arm using local anesthesia. Of the patients 8 received 1 and the remainder received 2 implants. Treatment with the antiandrogen flutamide or cyproterone acetate began 2 weeks before implant insertion and continued for up to 12 weeks. Testosterone, luteinizing hormone (LH) and prostate specific antigen were determined monthly, and a metastatic evaluation was performed every 6 months. RESULTS: LH and testosterone increased after flutamide administration and decreased after implant insertion. By day 28 LH and testosterone were completely suppressed. LH and testosterone decreased immediately after cyproterone acetate administration. Prostate specific antigen began to decrease during antiandrogen therapy and decreased further after implant insertion. One patient requested implant removal after 1 year for personal reasons and 1 died of an unrelated cause 18 months after insertion. Escape was demonstrated in 4 cases at 5, 10, 12 and 19 months, although LH and testosterone remained suppressed. Duration of treatment in the remaining 9 patients was between 21 and 30 months. LH and testosterone remained completely suppressed and prostate specific antigen levels were in the normal range. The clinical and biochemical response was identical in those who received 1 or 2 implants. At 12 months 8 patients were challenged at intermittent intervals for up to 24 months with a bolus of 100 microg. gonadotropin hormone-releasing hormone followed by 2 weeks of flutamide. The response was compared with that in untreated controls recently diagnosed with prostate cancer. Unlike controls there was complete LH suppression in the 8 challenged patients. CONCLUSIONS: A histrelin implant suppresses LH and testosterone in prostate cancer for up to 30 months. This finding represents a significant improvement over existing preparations, which must be administered at 1 to 3-month intervals.     

LHRH analogue for treatment of recurrent and refractory mastalgia

The LHRH analogue Zoladex was used to treat 21 premenopausal women with severe recurrent or refractory breast pain. Severity and pattern of mastalgia, whether cyclical or non-cyclical, was assessed using self-administered record cards. Symptom relief was achieved in 17 (81%) of the patients. This study showed Zoladex to be an effective short-term treatment for refractory and recurrent mastalgia.     

Effect of thyroid releasing hormone on bladder and urethral pressures

In order to explain the pathophysiology of urinary urgency frequency observed following the administration of thyroid releasing hormone (TRH) during thyroid function testing, simultaneous urethrocystometry was performed in six females before and after TRH administration, and in another five females before and after administration of normal saline (control group). Within a few minutes following TRH administration, a statistically significant and consistent drop in maximal urethral pressure and concomitant sensation of urinary urgency in the absence of significant changes in true detrusor pressure suggested the presence of a reflex neuronally mediated motor component to this sensory effect of urinary urgency. The absence of urethral and detrusor pressure changes in the control group reinforced the TRH-mediated origin of urinary urgency.