Reduced pituitary volume in children with short stature: clinical and radiological correlates

A retrospective evaluation of 80 cases of growth retardation evaluated at the H?pital Sainte-Justine of Montreal has revealed that 20 of them (25%; 15 boys and 5 girls) had a reduction of pituitary volume as revealed by high-resolution CT scanning of the pituitary gland. Of these patients, 8 had complete growth hormone (GH) deficiency, as evaluated by arginine infusion and L-Dopa-propranolol testing and nocturnal blood sampling, and 3 had GH neurosecretory dysfunction. Five patients had combined or multiple hormonal deficiencies. A statistically significant correlation was found between nocturnal plasma GH values and pituitary volumes. From this study it can be concluded that reduced pituitary volume is a frequent finding in growth-retarded children with hypopituitarism.     

Sub-clinical hypothyroidism in infertile Nigerian women with hyperprolactinaemia

Studies on the impact of subclinical hypothyroidism in infertility are scarce and this seeks to determine the proportion of infertile Nigerian women with hyperprolactinaemia that had subclinical hypothyroidism. Serum prolactin and thyroid stimulating hormone were determined using ELECSYS 1010 auto analyzer. Two hundred infertile women were evaluated and 67(33.7%) had hyperprolactinaemia. Subclinical hypothyroidism was observed in 14.9% of women with hyperprolactinaemia, 4.5% and 10.5% of women with primary and secondary infertility, while hyperprolactinaemia was observed in 29.9% and 70.1% in primary and secondary infertility respectively. Mean levels of thyroid stimulating hormone and prolactin were higher in secondary infertility than primary infertility. Subclinical hypothyroidism and hyperprolactinaemia were higher in secondary infertility than primary infertility. The ratio of proportions between hypothyroidism and hyperprolactinaemia was 1:7. Keywords: Sub clinical hypothyroidism, Hyperprolactinaemia, Primary infertility, Secondary infertility.     

Thyrotropin-secreting pituitary adenoma: a case report.

We report a 44-year-old male with a thyrotropin (TSH)-secreting pituitary adenoma. Based serum free triiodothyronine (FT3, 12.1 pmol/l) and free thyroxine (FT4, 28 pmol/l) were increased with normal basal TSH (3.1 mU/l). There was impaired TSH response to thyrotropin releasing hormone (TRH) test. Serum TSH was suppressed to 59% of the basal level after oral administration of 1.4 mg 3,3'-5-triiodothyroacetic acid (triac), whereas no suppression was observed after 75 micrograms daily administration of triiodothyronine (T3). Serum concentrations of alpha-subunit of TSH (TSH-alpha) and TSH-alpha/TSH molar ratio were high, being 1.95 micrograms/l, and 4.4, respectively. Pituitary CT and MRI scan showed the presence of a macroadenoma in the anterior lobe of the pituitary gland. Histopathology of the excised pituitary confirmed the diagnosis of a TSH-producing adenoma. A positive correlation between TSH and FT3 (r = 0.66, P less than 0.01) or FT4 (r = 0.54, P less than 0.01) was observed in serial sera obtained before and after operation.     

Bone mineral content in normally menstruating women with hyperprolactinaemia

Decreased bone density has been reported in women with hyperprolactinaemia due to pituitary tumours. We identified a number of seemingly healthy women with hyperprolactinaemia, i.e. a serum prolactin concentration exceeding 500 mU/l (25 micrograms/l) on three occasions, during a study in 1980/1981 of a representative population sample of greater than 1,400 women in seven different age strata (range 26-72 years). We compared vertebral bone mineral content and bone mineral areal content in 5 hyperprolactinaemic normally menstruating 50-year-old women with that of 6 controls matched for age and menstrual status but found no difference. Since the degree of prolactin elevation was similar in our study group to that previously reported for hyperprolactinaemic subjects with pituitary tumours and the time of exposure to raised hormone concentration appears to be of the same magnitude, other hormonal changes than hyperprolactinaemia per se seem to be the cause of low bone mineral content in women with hyperprolactinaemia and amenorrhoea.     

Prolactin and schizophrenia: clinical consequences of hyperprolactinaemia

Prolactin is a polypeptide hormone that is synthesized and secreted from specialised cells of the anterior pituitary gland, known as lactotrophs. The hormone was given it's name because extracts from the bovine pituitary gland caused growth of the crop sac and stimulated the elaboration of crop milk in pigeons, and promoted lactation in rabbits. Although prolactin is best known for the multiple effects it exerts on the mammary gland, it has over 300 separate biological activities not represented by its name. It sub serves multiple roles in reproduction other than lactation and is an important modulator of homeostasis in the mammalian organism. Hence Bern and Nicoll suggested renaming it "omnipotin or versatilin". Schizophrenia is a severe psychiatric disorder that affects approximately one percent of the population worldwide. It is well established that traditional typical anti-psychotics elevate prolactin levels. It is also agreed that the serum prolactin concentration is not elevated in patients with schizophrenia who are not receiving anti-psychotic medication. Hyperprolactinaemia has direct effects on the brain and on other organs. Direct consequences include galactorrhoea. Indirect consequences of hyperprolactinaemia include oligomenorrhoea and amenorrhoea, erratic or absent ovulation, sexual dysfunction, reduced bone mineral density and cardiovascular disease. With the advent of prolactin sparing anti-psychotics, ample consideration needs to be given to the physiological consequences of hyperprolactinaemia in schizophrenic patients. In this paper we will examine molecular biology, secretion and physiology of prolactin. The consequences of hyperprolactinaemia in humans including effects on fertility, sexual dysfunction, bone mineral density, cardiovascular disease, changes in psychopathology and movement disorders will be reviewed. The literature on the association between schizophrenia, anti-psychotic medication and hyperprolactinaemia and more specifically on the consequences of this hyperprolactinaemia in schizophrenic patients will also be reviewed.     

Bovine model for the study of reproductive aging in women: follicular, luteal, and endocrine characteristics

At present, there is no well-characterized animal model to study the effects of aging on fertility in women. The objectives of the study were to characterize age-related changes in ovarian and endocrine functions in old cows and to investigate the validity of a bovine model for the study of human reproductive aging. We tested the hypotheses that aging in cattle is associated with 1) elevated concentrations of gonadotropins and reduced concentrations of steroid hormones in systemic circulation and 2) increased recruitment of ovarian follicles during wave emergence. Daily ultrasonography was performed in 13- to 14-yr-old cows (n = 10) and their 1- to 4-yr-old daughters (n = 9) for one interovulatory interval to study ovarian function. Plasma samples were obtained every 12 h for determination of FSH, LH, progesterone, and estradiol concentrations. Circulating FSH concentrations were higher (P = 0.009) during follicular waves in old cows than in their daughters, but the number of 4- to 5-mm follicles recruited into a wave was lower (P = 0.04) in old cows. Plasma LH concentrations did not differ between groups (P = 0.4), but the ovulatory follicle in two-wave cycles was smaller in old cows (P = 0.04). Plasma estradiol concentrations were higher (P = 0.01) in old cows, and luteal phase progesterone tended to be lower (P = 0.1). We conclude that these changes are consistent with those reported for women approaching menopause transition. Therefore, our results validate the use of the bovine model to study reproductive aging in women.     

Anthropological and clinical characteristics in adolescent women with dysmenorrhea

The aim of this study was to examine the prevalence of dysmenorrhea in female adolescents and the influence of anthropological characteristics and lifestyle factors on menstrual pain. Two hundred and ninety seven girls from several elementary and secondary schools were interviewed about the presence of the menstrual pain, their age, height and weight, menarcheal age, menstrual cycles quality, smoking and sexual activity. There were 164 (55%) subjects with and one hundred and thirty three (45%) without dysmenorrhea. The adolescents with dysmenorrhea answered the questions about missing activities and taking pills for pain. No difference was observed between the girls with and the girls without dysmenorrhea in their chronological age, height, weight, menarcheal age, menstrual cycles quality, cigarette smoking and sexual activity. In the group of dysmenorrheic adolescents there was infrequent missing activities and bedrest, but missing school was observed in 22 percent and taking pills for pain was observed in 96 percent of the subjects. Young girls who experienced menstrual pain are good candidates for a prophylactic therapy, such as hormonal contraception. A replication of this study is needed for public health services in the future to improve the quality of life of the dysmenorrheic young women.     

Proliferating cell nuclear antigen (PCNA) expression in pituitary adenomas: relationship to the endocrine phenotype of adenoma

The expression of proliferating cell nuclear antigen (PCNA) correlates to cell proliferation and for this reason it is commonly considered as one of proliferation markers. Since proliferation rate is an important factor determining the tumor aggressiveness, the evaluation of PCNA index (the percentage of PCNA-immunopositive nuclei in the investigated tumor sample) is suggested as useful in predicting pituitary adenoma outcome. Seventy three unselected, surgically removed pituitary adenomas were immunostained with antibodies against the pituitary hormones or their subunits and against the proliferating cell nuclear antigen (PCNA). The highest PCNA index was found in ACTH-immunopositive tumors without the manifestation of the Cushing's disease ("silent" corticotropinomas). This value was significantly different in comparison to other adenoma subtypes including corticotropinomas manifesting themselves by Cushing's disease. The lowest PCNA index was noticed in monohormonal GH-secreting tumors. The adenomas which express more than one hormone (plurihormonal adenomas) seem to have a higher PCNA indices than monohormonal ones; the difference was significant in the case of mono- and plurihormonal prolactinomas. The recurrent tumors presented a higher mean PCNA index as compared to the primary tumors, although the difference was significant only in the case of prolactinomas. These findings suggest that the proliferative potential of pituitary adenomas is related to the tumor recurrence and hormone expression.     

LH- and FSH-secreting pituitary adenoma in a postmenopausal woman.

Gonadotropin secreting pituitary adenomas have been reported with increasing frequency in men, but they are still rarely recognized in women. We report a 52-year-old postmenopausal woman with LH- and FSH-secreting pituitary adenoma. She had increased LH (37.0 +/- 13.7 IU/l) (mean +/- SD) and FSH (109.9 +/- 26.7 IU/l) but these concentrations were within normal ranges in 80 postmenopausal women (LH: 29.7 +/- 18.3 IU/l, FSH: 104.0 +/- 43.9 IU/l). The administration of GnRH and conjugated estrogen resulted in normal response of LH and FSH. No abnormal response of gonadotropin to TRH and bromocriptine was observed. After transsphenoidal adenomectomy both LH and FSH decreased (LH: 11.1 +/- 4.2 IU/l, FSH: 37.0 +/- 9.6 IU/l). An immunocytochemical study revealed that the adenoma cells synthesize both LH and FSH. The rarity of gonadotropin secreting pituitary adenomas in women could be the result of greater difficulty in recognition due to an increase in serum gonadotropin in postmenopausal women.     

A pituitary specific point mutation of codon 201 of the Gs alpha gene in a pituitary adenoma of a patient with multiple endocrine neoplasia (MEN) type 1.

The DNA from a pituitary adenoma of a patient with multiple endocrine neoplasia (MEN) type 1 was analyzed to detect a point mutation of the Gs alpha gene (gsp) by the PCR direct-sequencing method. The patient had galactorrhea, amenorrhea and acromegalic features. Hormonal examination revealed high serum levels of PRL and GH. The tumor was histologically diagnosed as a mixed GH cell-PRL cell adenoma in which GH and PRL were produced by different cells. Sequence analysis of the DNAs extracted from paraffin sections of pituitary, parathyroid, and pancreas tumors demonstrated the substitution of thymidine for cytidine in codon 201 of the Gs alpha gene that resulted in replacement of arginine (CGT) with cysteine (TGT) only in the pituitary adenoma, but not in the parathyroid and pancreas tumors. These results suggest that a pituitary specific point mutational activation of the Gs alpha gene may be involved in the development of the pituitary adenoma in this patient.     

Pregnancy in patients presenting with hyperprolactinaemia.

Ninety-two pregnancies occurred in 76 hyperprolactinaemic patients treated with bromocriptine. Half conceived within three months of attempted conception. There was no evidence of an increased rate of spontaneous abortion, fetal abnormality, or multiple pregnancy; the three twin pregnancies occurred in women who were additionally treated with clomiphene and human chorionic gonadotrophin. Thirty-one patients had radiological evidence of a pituitary tumour; 14 with major radiograph changes in the pituitary fossa or serum prolactin concentrations greater than 100 ng/ml received pituitary irradiation before conception. None of the latter showed evidence of enlargement of the tumour during pregnancy. In contrast two of the four patients with similar tumours but who were not irradiated developed visual field defects, one with gross destruction of the pituitary fossa. Prophylactic treatment to limit subsequent tumour expansion during pregnancy in patients with prolactinomas is indicated, and pituitary irradiation before conception appears to be a safe and effective method to achieve this goal.     

Wiedemann-Beckwith syndrome: clinical, cytogenetical and radiological observations in 39 new cases.

Thirty-nine patients (82% under 1 year of age) with Wiedemann-Beckwith syndrome (WBS) were prospectively studied. To evaluate the somatometric data the normal range was set out at mean +/- 2 SD. The relevant physical findings were a characteristic face, non increased mean height and weight, normal head circumference, defective abdominal wall, a predominance of the upper segment, and tibial bowing. Mental retardation was documented in 5 cases but in only 1 it was related to hypoglycemia. The 32 cases karyotyped were normal. Since neonatal hypoglycemia is frequent (34.3% in our series) and potentially deleterious for the CNS we propose to monitor the glycemia every 6 h during the first 3 days in WBS newborns in order to correct glycemia below of 2.6 mmol/l (46.8 mg/dl) according to recent studies. The comparison with previous large series enabled us to precise the frequency, onset and evolution of the main stigmata.