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The relationship between plasma prolactin and testosterone levels in male hypogonadism.

Fifty seven male patients either complaining of poor sexual development, gynecomastia or dwarfism and signs of sexual infantilism were studied. Plasma prolactin (PRL) and testosterone (T) were estimated in all patients while 33 of them were also subjected to full pituitary function tests. Twelve of the latter had an elevated basal plasma cortisol or growth hormone which suggested the patient may have been "stressed"; the results were analyzed both excluding and including these patients. The remaining patients were divided into those with a plasma T less than 8.0 nmol/l (Group A, 25 patients) and those with a plasma T greater than 8.0 nmol/l (Group B, 20 patients). The results were compared with those from 18 normal men (Group C). The mean plasma PRL in group A (108.1 mU/l) was significantly lower than that in group B (181.5 mU/l, p less than 0.005) or group C (255.7 mU/l, p less than 0.001). The difference between groups A and B became much less (p less than 0.01) when results from the "stressed" patients were included but this did not affect the difference with group C. The mean plasma PRL in group B was also significantly lower (p less than 0.05) than that in group C but the significance of the difference disappeared when all the patients were included (p less than 0.2). In the patients there was a significant correlation between plasma and PRL plasma T (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Isolated corticotroph insufficiency associated to myasthenia gravis.

Myasthenia gravis, a neuromuscular junction autoimmune disease, may be associated to glandular autoimmune diseases such as adrenalitis. We report here the association of myasthenia gravis with a rare cause of adrenocortical deficiency, i.e. isolated corticotroph deficiency. The patient suffered from myasthenia gravis for 5 yr when she reported increased asthenia. Basal cortisol and ACTH levels were low. Metyrapone failed to increase ACTH and 11-desoxycortisol. Corticotropin-releasing hormone or tetracosactide failed to increase normally the cortisol levels. No other endocrine dysfunction or autoimmune disease could be detected. This observation enlarges the spectrum of endocrine diseases associated to myasthenia gravis and strengthens the need for careful endocrine examination.

Adrenocorticotropic Hormone↗

Evaluation of anterior pituitary function in hypertensive patients following inhibition of angiotensin II generation.

The Authors investigated anterior pituitary function in hypertensive patients in basal conditions and following a 15-day course of treatment with captopril, a drug which blocks the generation of Angiotensin II (Angio II). No differences were observed for any of the pituitary hormones except ACTH, whose response to hypoglycemia was significantly blunted by the pharmacological treatment. A possible role of Angio. II in modulating some aspects of pituitary function is proposed.

Adult↗

Effect of surgery and radiotherapy on visual and endocrine function in nonfunctioning pituitary adenomas.

The effect of surgery alone or followed by radiotherapy in recovering visual abnormalities, debulking tumor mass and restoring hormone impairments was evaluated in 84 patients with clinical nonfunctioning pituitary adenomas (NFPA) subjected to 1-10 yr follow-up. All patients underwent surgery via transsphenoidal (in 69) or transcranic-pterional approach (in 15). Radiotherapy was performed after surgery in 59 of 72 patients with incomplete tumor removal. The assessment of pituitary function was performed in all patients before and every 1-2 yr after surgery and/or radiotherapy. Radiological and ophthalmologic assessment was performed before and 3, 6 and 12 months after surgery, then yearly. At diagnosis, headache and visual disturbances occurred in 63 and 58 patients, respectively, while deficiency of GH, TSH, ACTH, FSH, LH and ADH was documented in 55, 7, 19 47 and 6 patients, respectively. After surgery, gonadal function recovered in 12 women, visual disturbances improved in 43 patients (15 regained normal vision), pituitary function improved in 8 of 62 patients, worsened in 34 patients. At MRI, complete tumor removal was documented in 12 of 84 patients. After surgery alone, tumor regrowth was observed in 7 patients between 3-7 yr. After radiotherapy, vision improved in 9, remained unchanged in 49 and worsened in 1 of 59 patients. After radiotherapy, tumor regrowth was documented in 9 patients between 2-12 yr and the prevalence of hypopituitarism raised from 28.8% to 92% after 1 and 10 yr. In conclusion, surgery alone is effective only in a minority of patients (14.3%) and radiotherapy causes hypopituitarism in rather the totality of patients after 10 yr. The prevalence of tumor regrowth was similar in irradiated ones (15%) and non irradiated patients (28%; chi(2), p = 0.4). Therefore, a careful radiological followup is suggested after surgery so that radiotherapy can be performed promptly on the basis of clinical data, tumor regrowth and/or invasiveness documented at histology.

Adenoma↗

Primary intrasellar mixed germ-cell tumor with precocious puberty and diabetes insipidus.

We report an 8-year-old boy with a primary intrasellar mixed germ-cell tumor who underwent the trans-sphenoidal approach for tumor removal. Initially he suffered from diabetes insipidus. Precocious puberty and left abducens nerve palsy were also observed. Elevation of serum testosterone, beta-human chorionic gonadotropin (HCG), and alpha-fetoprotein (AFP) were found on admission. The histological study revealed mixed cellular types of tumor including germinoma, choriocarcinoma, embryonic cell carcinoma, and teratoma. Postoperative radiation to a total of 5000 cGy was performed. Adjuvant chemotherapy was administered before and after radiation. The boy was disease-free during a 6-month follow-up period. Follow-up magnetic resonance imaging showed no presence of tumor. The signs of precocious puberty disappeared, and the diabetes insipidus was easily controlled. The abducens nerve regained normal function. Serum HCG, AFP, and testosterone levels all returned to normal. Serum antidiuretic hormone increased to reach the lower limit of the normal range.

Child↗

Basal interhemispheric supra- and/or infrachiasmal approaches via superomedial orbitotomy for hypothalamic lesions: preservation of hypothalamo-pituitary functions in combination treatment with radiosurgery.

Although several approaches to the hypothalamus have been used, none is able to give full views of the hypothalamus. The risk of permanent morbidity for hypothalamo-pituitary functions is still high, especially in patients with craniopharyngioma. Basal interhemispheric supra-chiasmal or infra-chiasmal approaches via superomedial orbitotomy were developed for better visualization of the hypothalamus. Operative techniques and results, including combination treatment with radiosurgery, are reported. Twelve patients with tumors compressing the hypothalamus upward or extending into the III ventricle, or both, were operated on: 3 tumors were removed totally, 6 tumors subtotally and 3 tumors partially. Six patients received radiosurgery for residual tumor. Four patients with hypopituitarism preoperatively required oral corticosteroids and thyroid hormones postoperatively. The basal interhemispheric approach via superomedial orbitotomy is useful for better visualization of the hypothalamus and preservation of hypothalamo-pituitary functions.

Adenoma↗

Lymphocytic hypophysitis presenting with diabetes insipidus in a 14-year-old girl: case report and review of the literature.

UNLABELLED: Lymphocytic hypophysitis is a rare disorder predominantly affecting females during the antepartum or postpartum period. It is characterized by destruction and lymphocytic infiltration of the pituitary gland, probably by an autoimmune process, leading to a pituitary mass lesion and/or various degrees of hypopituitarism. The lesion is usually confined to the adenohypophysis. Posterior pituitary gland or stalk involvement is rare, although patients presenting with diabetes insipidus have been reported. We describe a girl aged 13 years 9 months with lymphocytic hypophysitis who presented with diabetes insipidus and secondary amenorrhea. MRI of the brain revealed a 1 cm enhancing mass in the pituitary stalk. A biopsy of the mass by right pterional craniotomy showed lymphocytic infiltration without neoplastic cells or granuloma formation. To our knowledge, this is the youngest reported patient with a diagnosis of lymphocytic hypophysitis. In this case report, her clinical presentation is discussed along with a review of the literature. CONCLUSION: We present the first childhood case of lymphocytic hypophysitis which is an autoimmune inflammatory disorder of the pituitary gland. Although this is a rare condition in adults, it also needs to be considered in the pediatric population. Conservative management is preferred unless there are signs of increased intracranial pressure. Most importantly, close monitoring for multiple hormone deficiencies is indicated in this condition.

Adolescent↗

Long-term efficacy of bromocriptine in macroprolactinomas and giant prolactinomas in men.

We prospectively analyzed presentations and long-term therapeutic responses to bromocriptine (BRC) in 29 newly diagnosed men with macroprolactinomas including 14 patients with 'giant prolactinoma'. Clinical symptoms, prolactin (PRL) levels and tumor size on MRI were measured before BRC and sequentially thereafter. The duration of follow-up were 6 to 96 (30.7 +/- 14.4) months. Pretreatment PRL ranged between 124 and 29200 ng/mL (1698 +/- 857.1) and tumor volume was between 2.81 and 132 cm(3) (21.1 +/- 24.3). Baseline PRL levels did not correlated with tumor volume (r = 0.45, P > 0.05). Significant decrease (P = 0.0003) in PRL, at least 96% of the pretreatment value from 1698 +/- 857.1 ng/mL to 42.4 +/- 30.6 ng/mL occurred in 26 patients. Persistent normalization of PRL levels (< 16 ng/mL) for at least 6 months was achieved in 12 patients (40.8%). Twenty-two patients (74.8%) achieved significant tumor shrinkage (P = 0.005) at study completion. An improvement in visual field defects (VFD) and restoration of libido and potency was observed in 40% and 33.3%, respectively. Trans-sphenoidal / trans-frontal pituitary surgery was performed in 9 patients (31%) for various reasons: pituitary apoplexy in 1, CSF rhinorrhea in 2, increasing prolactin in spite of BRC therapy in 3, and intolerant /resistant to BRC in 3 patients. These data suggest that, in male macro- and giant prolactinomas, dopamine agonists represent the first-line therapy effective in reducing PRL, restoration of libido and potency, improvement of VFD and determining tumor shrinkage.

Adolescent↗

Primary empty sella syndrome with visual field defects.

A patient with an enlarged, asymmetric sella turcica and visual field defects suggestive of a pituitary or parasellar tumor underwent extensive roentgenographic and pituitary function studies. No abnormalities in pituitary luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, ACTH, prolactin or vasopressin secretion were detected. Growth hormone secretion was provoked by arginine infusion but not by hypoglycemia. Pneumoencephalography revealed air in the sella turcica, and no evidence of tumor. Thus, an enlarged sella turcica in a patient with visual field defects but normal pituitary function may suggest the presence of an "empty sella syndrome."

Humans↗

Effect rates of different modalities for treatment of prolactin adenomas.

Results of treatment of 963 patients with prolactin adenomas described in the literature were reviewed. The patient population was stratified into four subgroups: women and men with serum prolactin levels above and below 100 ng/ml for each of the treatment modalities: transsphenoidal surgery, bromocriptine, heavy ion radiation, conventional radiation, and transsphenoidal surgery plus conventional radiation. The five largest series within each subgroup were included. Success rates and recurrence rates were calculated for: (1) reduction of tumor size, (2) normalization of serum prolactin levels, and (3) normalization of other pituitary functions. Complication rates were calculated for procedural impairment of other pituitary functions. Transsphenoidal surgery was found to be the most effective treatment for lasting control, and bromocriptine for temporary control, of prolactin adenomas. Recurrent adenomas were most effectively treated by transsphenoidal surgery if serum prolactin levels were below 100 ng/ml. If serum prolactin levels were above 100 ng/ml, bromocriptine was the most effective treatment. Heavy ion radiation, with success rates comparable to those of transsphenoidal surgery and bromocriptine, but with lower recurrence rates, may eventually prove the most effective treatment of all.

Adenoma↗

Primary radiotherapy of prolactinomas. Eight- to 15-year follow-up.

Eight women with amenorrhea, galactorrhea, and hyperprolactinemia, of whom six had macroadenomas and two had microadenomas, were treated with conventional (cobalt-60) external radiotherapy, and their progress was monitored for eight to 15 years. Normoprolactinemia was established in five of these patients after two to 13 years (median, nine years). A recurrence was treated surgically in one patient, and stable prolactin values and roentgenographic features have been maintained in two patients. Hypopituitarism has developed in only one patient to date, and no other complications of radiotherapy have been observed. These findings, together with the few previous reports on the long-term effects of radiotherapy on macroprolactinomas, have been compared with the long-term results following surgery or dopamine agonist therapy. The normalization of prolactin values is considerably delayed following radiotherapy compared with the other two therapeutic modalities. However, radiotherapy affords permanent normalization without recurrence in a larger percentage of patients than does surgery and avoids the considerable ongoing cost and inconvenience of daily drug ingestion. The long-term development of hypopituitarism appears to be an acceptably small risk of radiotherapy. Thus, conventional radiotherapy is an attractive treatment option, particularly for macroprolactinomas; adjunctive bromocriptine can be used while awaiting the longer-term benefits of radiotherapy.

Adult↗

Premature menopause. I. Etiology.

The premature menopause syndrome has been regarded as one of the organ-specific autoimmune disorders because circulating antibodies to ovarian tissue have been demonstrated. Fifteen women with spontaneous cessation of menses after initial menarche before they were 35 years old were seen between 1975 and 1977. Increased serum levels of gonadotropin and failure of estrogen secretion were documented. Serum from each woman was examined for antibodies to normal ovary. Proteins from ovaries of normal premenopausal women were extracted and iodinated with 125I. The labeled proteins were incubated with sera for 48 hours, after which goat antihuman gamma-globulin was added and allowed to incubate for 72 hours. The precipitate was washed and evaluated for radioactive label. The binding of antibodies increased in the sera of patients with the premature menopause syndrome, compared with the control sera. This suggests that the etiology of premature menopause may be mediated by circulating antibodies to ovarian tissue.

Adult↗

Inhibition of corticotrophin releasing factor secretion in the pentobarbitone-morphine-treated rat.

The concentrations of ACTH in the plasma and adenohypophysis and corticotrophin releasing factor (CRF) in the hypothalamus were determined and the functional capacities of the adenohypophysis and hypothalamus assessed in male rats treated with pentobarbitone and morphine. A single injection of morphine increased markedly the concentrations of ACTH in both the plasma and the adenohypophysis and the CRF content in the hypothalamus. When the opiate was given to rats injected 10 min previously with sodium pentobarbitone its effects were substantially reduced and the hypothalamo-pituitary-adrenocorticotrophic response to stress was abolished. The functional activity in vitro of pituitary tissue removed from control rats was not affected by the addition to the incubation medium of pentobarbitone and/or morphine. Pituitary glands of drug-treated rats also responded normally both in vivo and in vitro, with respect to ACTH secretion, to hypothalamic extracts prepared from control animals, CRF-41 and arginine vasopressin (AVP). On the other hand, hypothalami removed from pentobarbitone/morphine treated rats showed a marked reduction in their ability to secrete CRF in response to acetylcholine or 5-hydroxytryptamine as also did hypothalami from control animals after preincubation with pentobarbitone and/or morphine. The results suggest that the hypothalamus is an important site of action of pentobarbitone and morphine in modulating the functional activity of the hypothalamo-pituitary-adrenocortical system and are in accord with the view that the pentobarbitone/morphine-treated rat is suitable for the detection and quantification of potential corticotrophin releasing factors.

Adrenocorticotropic Hormone↗

Pituitary-testicular axis abnormalities in immature male hypothyroid rats.

The pituitary-testicular disturbances which follow the onset of hypothyroidism were studied in immature male Wistar rats rendered hypothyroid by treatment with methimazole (MMI) given in drinking water, starting at 40 days of age. Half of the animals continued on MMI (MMI group) up to 140 days of age; the remaining rats were withdrawn MMI at 100 days and injected thereafter s.c. with 3 micrograms of T3 daily, during the last 40 days (MMI + T3 group). Ten rats were used as controls (C group). Hypothyroidism induced in immature animals significantly decreased serum T4, T3, LH, PRL, and testosterone levels, and also impaired the normal growth of body and sex accessory glands. T3 replacement therapy helped to normalize serum hormonal levels, but the body and sex accessory gland weights were not fully corrected. Hypothyroidism also reduced the [125I]LH/hCG binding sites of testicular homogenates. T3 replacement was not able to improve the binding; nonetheless, the hormone-receptor affinity constant remained unaltered among the groups. Leydig cell responsiveness to hCG stimulation in vitro (0-82 nM) showed impaired testosterone production in the MMI group (25% of that found in the C group) and also in the MMI + T3 group (80% of that found in the C group). These data demonstrate that induction of hypothyroidism in the immature male rat leads to alterations in serum LH, PRL and testosterone levels, and suggest that thyroid hormones have a modulating action on the testis as far as LH-mediated testosterone secretion is concerned.

Animals↗

Content of mutant mitochondrial DNA and organ dysfunction in a patient with a MELAS subgroup of mitochondrial encephalomyopathies.

A point mutation of mitochondrial tRNALeu(UUR) gene is responsible for a MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) subgroup of mitochondrial encephalomyopathies. In most cases, the mutant mitochondrial DNA (mtDNA) coexists with normal mtDNA in a heteroplasmic manner. In order to quantify the content of mutant mtDNA, we developed a quantitative method of PCR. Using this method, the distribution of the mutant mtDNA was examined in 32 different tissues among 18 autopsied organs from a patient with MELAS, who had shown hypophyseal dysfunction. The percentage of the mutant mtDNA at nucleotide number 3243 in each tissue was ranged between 22% and 95%. The content of the mutant mtDNA was at the highest (95%) in the hypophysis and higher in the cerebral cortex than in the white matter. This study shows a possible correlation of tissue dysfunction with accumulation of the mutant mtDNA within the brain.

Adult↗