Primary empty sella syndrome and amenorrhea.

The empty sella syndrome is defined anatomically and radiologically. A case report of an amenorrheic patient who was diagnosed as having the primary empty sella syndrome is presented. Its pathogenesis, clinical profile, and endocrine relationships are discussed. Specific reference is directed toward the capability of the empty sella syndrome to produce pituitary impairment and possibly amenorrhea.     

Hypothalamic-pituitary function and radiographic evaluation of women with hyperprolactinemia and an "empty" sella turcica.

A primary "empty" sella may be associated with significant hypothalamic-pituitary dysfunction. This report characterizes the endocrinologic and radiographic findings in six patients with hyperprolactinemia (range 34.3 to 1,170 ng/ml) ultimately found to have an enlarged empty sella. Lateral skull x-ray films and thin-section tomograms were suggestive of pituitary tumors in all patients. Four patients underwent transphenoidal sellar exploration after pneumoencephalography (PEG) failed to demonstrate air within the sella. The inability of PEG to demonstrate an empty sella in two patients was explainable on the basis of an intact diaphragma sellae with previous transient intrasellar pathology responsible for the sellar enlargement. Dynamic hypothalamic-pituitary testing yielded no consistent pattern of response. These studies suggest that an empty sella: (1) may be associated with hyperprolactinemia, regardless of etiology, (2) is not diagnosable by dynamic hormonal testing, and (3) may be indistinguishable from a pituitary tumor by current radiographic techniques.     

Virilizing oncocytic adrenocortical carcinoma: clinical and immunohistochemical studies

Context: Oncocytic tumors of the adrenal cortex are rare, mostly nonfunctioning and benign.

Setting: Report virilizing oncocytic adrenocortical carcinoma in a 50-year-old woman.

Patient: She presented a recent and progressive virilization syndrome, associated with high blood pressure. Hormonal evaluation showed elevated serum testosterone and delta-4-androstenedione levels, normal urinary free cortisol level and incomplete suppression of cortisol at the 1?mg dexamethasone suppression test. CT scan of the abdomen revealed a 35?mm left adrenal mass.

Intervention: The patient underwent a left adrenalectomy, and the histological study showed a 3?cm oncocytic adrenocortical carcinoma with signs of malignancy.

Results: Immunohistochemical study revealed that tumor cells expressed the steroidogenic enzymes involved into androgen synthesis (3βHSD and P450c17α), P450 aromatase and luteinizing hormone (LH) receptors. Post-operatively, signs of virilization improved rapidly, serum testosterone and delta-4-androstenedione levels returned to normal, as did the dexamethasone suppression test. During follow-up CT-scan and 18-FDG PET/CT showed a right ovary mass, corresponding to a follicular cyst associated with hyperthecosis. The patient is alive with no recurrence 48 months after adrenal surgery.

Conclusion: Oncocytic adrenocortical carcinomas, although extremely rare, should be considered in women with a virilization syndrome. In this woman immunohistochimical studies revealed the presence of steroidogenic enzymes involved into androgen synthesis and aromatization, and LH receptors could be implicated in this pathology.     

The incidence of non-classical 21-hydroxylase deficiency in hirsute adolescent girls.

Non-classical adrenal hyperplasia due to 21-hydroxylase enzyme deficiency (NC21OHD) causes hirsutism, acne and menstrual irregularities in women. Clinically, patients with NC21OHD may be indistinguishable from other hyperandrogenic women, as they all present with similar symptoms. An elevated response of cortisol precursors like 17 alpha-hydroxyprogesterone (17-OHP) to ACTH stimulation is a valuable diagnostic criteria. In this study, 32 hirsute adolescent girls, aged 13-19 years, underwent i.v. adrenocorticotrophic hormone (ACTH) (Synacthen 0.25 mg) stimulation test. The results were compared with those of the controls. The plasma levels of 17 alpha-hydroxyprogesterone, cortisol, dehydroepiandrosterone sulphate (DHEA-S), androstenedione, testosterone, follicle stimulating hormone (FSH), luteinizing hormone (LH) and prolactin were established before, and 60 min after the infusion of ACTH to both patients and controls. Six patients demonstrated an increase in both the 17 alpha-hydroxyprogesterone levels and the 17 alpha-hydroxyprogesterone/cortisol ratio on ACTH stimulation, almost twice that of the mean +/- 2SD in the control group and ten times that in one patient. Six patients with abnormal elevation of 17 alpha-hydroxyprogesterone were considered heterozygotes for 21-hydroxylase enzyme deficiency, and one patient was presumed to have NC21OHD. Human leukocyte antigen (HLA) analysis supported these diagnoses. In this study, the incidence of NC21OHD in hirsute adolescent girls in our population was investigated, and NC21OHD was found in only one of 32 patients.     

Twin pregnancy using recombinant gonadotropins in a woman with hypogonadotropic hypogonadism.

In women with hypogonadotropic hypogonadism both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are required to induce optimal follicular growth and steroidogenesis. The development of molecular genetic technology has led to the availability of recombinant FSH and LH for the induction of follicular growth and ovulation. We describe a first case of a twin pregnancy in a 36-year-old patient presenting with primary hypogonadotropic amenorrhea and empty sella syndrome and treated with recombinant FSH and LH. This therapy led to the maturation of two follicles, both of which were fertilized. A twin pregnancy ensued and two normal infants were delivered.     

Brain tumor presenting as anorexia nervosa in a 19-year-old man.

Slow-growing brain tumors can produce disturbances of food intake and endocrine dysfunction. We report a case of slow-growing midline brain tumor in a patient with clinical presentation of anorexia nervosa (AN). A 19-year-old man was referred from a general practitioner to a psychiatric clinic due to illness behavior and psychopathological characteristics of AN. His body weight had decreased from 52 kg to 40 kg within 6 months. Laboratory tests showed hypernatremia (160 mmol/L), adrenal insufficiency (adrenocorticotrophic hormone, 11.4 pg/mL; 8 am cortisol, 1.4 microg/dL; 4 pm cortisol, 11.4 microg/dL) and hypogonadotropic hypogonadism (testosterone < 0.5 ng/mL, follicle-stimulating hormone < 0.1 mIU/mL, luteinizing hormone < 0.7 mIU/mL). Brain magnetic resonance imaging showed an extensive mass lesion at suprasellar, hypothalamic region, third ventricle, pineal region, lateral ventricle, and corpus callosum. Owing to central herniation during physical assessment, he died of unknown intracranial pathology. This case suggests that an intracranial tumor near the hypothalamus should be included in the differential diagnosis of AN. Any male adolescent with the clinical impression of AN should receive periodic re-evaluation, including neurological, endocrinological and, if necessary, neuroimaging study.     

The clinical significance of metastases to the adrenal glands

Seven patients, four of whom subsequently proved to have bilateral and three, unilateral adrenal metastases, were evaluated regarding adrenal activity. Three of the patients had clinical signs and symptoms similar to those usually associated with manifest adrenal insufficiency. Massive tumor growth, with less than 20 per cent residual amounts of apparently normal adrenal tissue, was found in three of the four patients with bilateral metastases. The metastases in the fourth patient were smaller and could only be detected microscopically. Evaluation of the adrenal activity included the determination of cortisol levels in plasma at 8 am, 2 pm and 8 pm; single dose dexamethasone suppression test with adrenocorticotropic hormone stimulation, and analysis of 24 hour urinary excretion of epinephrine and norepinephrine. In all seven patients, the plasma cortisol levels, dexamethasone suppression--adrenocorticotropic hormone stimulation test results and urinary excretion of epinephrine and norepinephrine were similar to those found in comparable patients without adrenal metastases. Thus, the metastases did not seem to be of any clinically significant importance for the patients. It was concluded that, apparently, only minimal amounts of residual adrenal tissue are sufficient to maintain, for basic conditions, normal production of cortisol and of epinephrine and to even respond to stress.     

Multiple courses of betamethasone to enhance fetal lung maturation do not suppress neonatal adrenal response

Objective: Our purpose was to evaluate the neonatal adrenal gland by provocative testing in neonates of mothers who had received multiple courses of betamethasone to enhance fetal lung maturity. Study Design: Infants of mothers who had received ≥3 courses of betamethasone for fetal lung maturation were enrolled in the study. Twenty-four hours after delivery a baseline serum cortisol concentration was obtained. A synthetic adrenocorticotropic hormone (Cortrosyn) was administered (0.25 mg/1.73 m²). Two hours later a second serum cortisol concentration was obtained. An increase in serum cortisol in response to Cortrosyn was considered a positive test result. Nominal data were compared by means of the Student t test. Results: There were 9 infants enrolled in the study. The mean number of betamethasone treatment cycles was 4.8 ± 1.09. The mean baseline cortisol level was 2.23 ± 0.52 μg/dL, and the mean post–adrenocorticotropic hormone cortisol level was 9.86 ± 1.70 μg/dL. All neonates had a positive adrenocorticotropic hormone test result. Stepwise linear regression showed no association between the number of courses of betamethasone treatment cycles and the post–adrenocorticotropic hormone cortisol concentration. Conclusion: Multiple weekly treatment cycles of betamethasone for fetal lung maturity administered between 24 and 34 weeks’ gestation do not appear to cause adrenal suppression. (Am J Obstet Gynecol 1999;180:1349-53.)     

Synchronous diagnosis of multiple tumours in a postmenopausal woman

We report an unusual case of a postmenopausal woman that was diagnosed with multiple tumours derived from different embryogenic tissues. She presented with postmenopausal vaginal bleeding. Clinical examination revealed a large pelvic mass, tender on palpation. Serum CA-125 level was elevated at 8,985 kU/l (normal range 0–35). A CT scan showed a malignant-appearing right ovarian mass with a peritoneal nodule, small amount of free fluid in the pelvis and evidence of a colonic intussusception. The patient underwent total abdominal hysterectomy, bilateral salpingo-ophorectomy, partial omentectomy and right hemicolectomy with side-to-side anastomosis. Histopathology showed a Grade 3 endometrial adenocarcinoma. Both ovaries were completely replaced by partially necrotic poorly differentiated endometrioid adenocarcinoma. Small deposits of metastatic adenocarcinoma were seen within the omentum. Sections from the retroperitoneal mass showed a low-grade liposarcoma. A large polypoid tumour within the right colon was a tubulo-villous adenoma.     

Characteristic features of 20 patients with Sheehan's syndrome.

Sheehan's syndrome occurs as a result of ischemic pituitary necrosis due to severe postpartum hemorrhage. The aim of the present study was to determine the clinical characteristics of Sheehan's syndrome in 20 patients (mean age 60.15 +/- 3.41 years) with typical obstetric history. The mean duration between time of diagnosis and date of the last delivery was 26.82 +/- 2.52 years (range 2-40 years). All patients had a history of massive hemorrhage at delivery and physical signs of Sheehan's syndrome. Fourteen patients (70.0%) lacked postpartum milk production and did not menstruate following delivery. Baseline and stimulated anterior pituitary hormone levels were measured in all patients. According to the hormonal values, 18 (90.0%) patients had secondary hypothyroidism, 11 (55.0%) had adrenal failure and all of them had hypogonadism, prolactin and growth hormone deficiency. Hyponatremia was present in seven patients (35.0%). Total or partially empty sella was revealed in all patients by magnetic resonance imaging. Diabetes insipidus was not found in any patient. We found that lack of lactation in the postpartum period and early menopause seemed the most important clues for diagnosis of Sheehan's syndrome, and inadequate prolactin and gonadotropin responses to stimulation tests were the most sensitive diagnostic signs in patients with severe postpartum hemorrhage.     

Plasma adrenocorticotropic hormone and cortisol and adrenal blood flow during sustained hypoxemia in fetal sheep

We examined the effect of sustained hypoxemia with progressive acidemia on pituitary-adrenal endocrine function (adrenocorticotropic hormone, cortisol) and on adrenal blood flow in fetal sheep. Hypoxemia was induced by the maternal sheep breathing a gas mixture containing 9% oxygen, with 3% carbon dioxide added. Induced hypoxemia resulted in a progressive fetal metabolic acidosis but with little change in maternal pH. During induced hypoxemia there was little change in maternal plasma adrenocorticotropic hormone or cortisol level. Fetal adrenocorticotropic hormone and cortisol increased to peak values within 2.8 hours of induced hypoxia but by 7.2 hours had begun to fall to values that were not significantly different from those at 1.4 hours. Fetal adrenal blood flow (microsphere technique) also increased significantly and remained elevated throughout the duration (7.2 hours) of hypoxemia. The maximum fetal adrenal blood flow achieved during hypoxemia was significantly correlated with the basal (prehypoxemia) flow to the adrenals. We conclude that the changes in fetal adrenocorticotropic hormone, cortisol, and adrenal blood flow seen in short-term hypoxemia are reproduced during sustained hypoxemia with acidemia. Furthermore, the noted rise in the fetal adrenocorticotropic hormone level may be an important factor contributing to the increase in adrenal blood flow during hypoxemia.     

Six-month oral dehydroepiandrosterone supplementation in early and late postmenopause.

The adrenal production of the delta 5-androgens, dehydroepiandrosterone (DHEA) and its sulfate ester dehydroepiandrosterone sulfate (DHEAS), declines linearly with aging. The evidence that DHEA or DHEAS administration may alleviate some of the problems related to aging has opened new perspectives for clinical research. The present study aims to investigate the effects of a 6-month DHEA supplementation in early and late postmenopausal women, with normal or overweight body mass index (BMI), on the level of circulating steroids, sex hormone binding globulin (SHBG), beta-endorphin and gonadotropins, and on the adrenal gland response to dexamethasone suppression and adrenocorticotropic hormone (ACTH) stimulation. Early postmenopausal women (50-55 years) both normal weight (BMI 20-24, n = 9) and overweight (BMI 26-30, n = 9) and late postmenopausal women (60-65 years) both of normal weight and overweight, were treated with oral DHEA (50 mg/day). Circulating DHEA, DHEAS, 17-OH pregnenolone, progesterone, 17-OH progesterone, allopregnenolone, androstenedione, testosterone, dihydrotestosterone, estrone, estradiol, SHBG, cortisol, luteinizing hormone, follicle stimulating hormone and beta-endorphin levels were evaluated monthly and a Kupperman score was performed. The product/precursor ratios of adrenal steroid levels were used to assess the relative activities of the adrenal cortex enzymes. Before and after 3 and 6 months of therapy, each women underwent an ACTH stimulating test (10 micrograms i.v. in bolus) after dexamethasone administration (0.5 mg p.o.) to evaluate the response of cortisol, DHEA, DHEAS, androstenedione, 17-OH pregnenolone, allopregnanolone, progesterone and 17-OH progesterone. The between-group differences observed before treatment disappeared during DHEA administration. Levels of 17-OH pregnenolone remained constant during the 6 months. Levels of DHEA, DHEAS, androstenedione, testosterone and dihydrotestosterone increased progressively from the first month of treatment. Levels of estradiol and estrone significantly increased after the first/second month of treatment. Levels of SHBG significantly decreased from the second month of treatment only in overweight late postmenopausal women, while the other groups showed constant levels. Progesterone levels remained constant in all groups, while 17-OH progesterone levels showed a slight but significant increase in all groups. Allopregnanolone and plasma beta-endorphin levels increased progressively and significantly in the four groups, reaching values three times higher than baseline. Levels of cortisol and gonadotropins progressively decreased in all groups. The product/precursor ratios of adrenal steroid levels at the sixth month were used to assess the relative activities of the adrenal cortex enzymes and were compared to those found before therapy. The 17,20-desmolase, sulfatase and/or sulfotransferase, 17,20-lyase and 5 alpha-reductase activities significantly increased, while the 3 beta-hydroxysteroid-oxidoreductase activity did not vary. On the contrary, the 11-hydroxylase and/or 21-hydroxylase activities showed a significant decrease after 6 months of treatment. In basal conditions, dexamethasone significantly suppressed all the adrenal steroids and this suppression was greater after 3 and 6 months of treatment for DHEA, DHEAS and allopregnanolone, while it remained unchanged for other steroids. Before treatment, ACTH stimulus induced a significant response in all parameters; after the treatment, it prompted a greater response in delta 5- and delta 4-androgens, progesterone and 17-OH progesterone, while cortisol responded less in both younger and older normal-weight women. The endometrial thickness did not show significant modifications in any of the groups of postmenopausal women during the 6 months of treatment. Treatment with DHEA was associated with a progressive improvement of the Kupperman score in all groups, with major effects on the vasomotor symptoms in     

Concurrent papillary thyroid cancer with pituitary ACTH-secreting tumor.

Concomitant thyroid cancer with pituitary tumor is uncommon. This study reports a case of advanced papillary thyroid carcinoma with pituitary adrenocorticotropic hormone (ACTH)-secreting tumor. A 58-year-old male patient had thyroid cancer in 1991 and presented with headache caused by pituitary tumor with apoplexy in 1993. Due to hypopituitarism, the patient underwent radioactive iodide ((131)I) for detection and treatment of metastatic thyroid cancer after the use of recombinant human thyroid-stimulating hormone (rhTSH) in 2000. During follow-up for thyroid cancer, (201)thallium scan proved to be an effective tool for detecting metastatic thyroid cancer in the patient without pituitary TSH reserve. Pituitary ACTH-secreting tumor was confirmed in 2001 based on the high serum ACTH level and positive immunohistochemical stain for ACTH. The patient had no Cushingoid features. Moreover, serum ACTH levels were 337 and 232 pg/mL with normal serum cortisol and urine-free cortisol. Although the patient underwent three operations and a total of 370 mCi (131)I therapy for recurrent thyroid cancer, the cancer continued to progress. Finally, the patient died of pneumonia with septic shock 12 years after the diagnosis of thyroid cancer.     

A case of coexistence of polycystic ovary syndrome and ovarian carcinoma]

There was a case of carcinoma of the ovary that coexisted with PCO syndrome in young, 25 years old woman. After clinical examination and USG doctors suspected PCO syndrome and hydrosalpings that is why the patient underwent an operation. In intraoperative histopathological examination bilateral adenocarcinoma were found. In prophylactic examination of patient's mother ovarian tumour was found that is also turned out to be an adenocarcinoma.     

Long-term low-dose oral administration of dehydroepiandrosterone modulates adrenal response to adrenocorticotropic hormone in early and late postmenopausal women.

OBJECTIVE: The aging process is associated with a decline in the circulating Delta5-androgen dehydroepiandrosterone (DHEA) and its sulfate ester, dehydroepiandrosterone sulfate (DHEAS). The present study aimed to evaluate the effects of a long-term (12 months) oral DHEA administration (25 mg/day) on adrenal function, before and after 3, 6 and 12 months of treatment. METHOD: Postmenopausal women belonging to two age groups, 50-55 years (n = 10) and 60-65 years (n = 10), were studied. Adrenal function was assessed in basal conditions, after suppression with dexamethasone (DXM) and following a stimulation test with adrenocorticotropic hormone (ACTH) (10 microg bolus). Serum levels of DHEA, DHEAS, androstenedione (Delta4-A), allopregnanolone, 17-hydroxyprogesterone (17-OHP) and cortisol were measured and the effects of DHEA supplementation on specific adrenal enzymatic pathways were evaluated by calculating precursor/product ratios (17-OHP/cortisol, 17-OHP/Delta4-A, DHEA/Delta4-A and DHEA/DHEAS). RESULTS: DHEA supplementation annulled the age-related differences in DHEA and DHEAS levels and induced a marked increase in all steroids, except for cortisol, after 3-6 months of treatment. Serum cortisol levels decreased from the 3rd month, both in younger and older subjects. DHEA supplementation did not affect DXM-induced suppression of adrenal steroidogenesis. During the treatment period all adrenal androgens and progestins showed a significant increase in their response to ACTH, while the cortisol response decreased significantly. The results suggest a significant DHEA-induced change in adrenal enzymatic activities, as also evidenced by the change in precursor/product ratios during therapy. CONCLUSION: Chronic DHEA administration is capable of modifying circulating levels of androgens and progestins in both early and late postmenopausal women by modulating the age-related changes in adrenal function.     

Effects of two oral contraceptive combinations, 0.125 mg desogestrel + 0.050 mg ethinylestradiol and 0.125 mg levonorgestrel + 0.050 mg ethinylestradiol on the adrenal function of healthy female volunteers

The effects of the oral contraceptive combinations of 0.125 mg desogestrel + 0.050 mg ethinylestradiol (EE), and of 0.125 mg levonorgestrel + 0.050 mg EE on serum cortisol and the urinary excretion of 17-oxogenic steroids and free cortisol were studied in 16 healthy females. Adrenal responsiveness was studied by the metyrapone test. Both contraceptive combinations increased (P less than 0.001) serum cortisol concentrations but the rhythmic fluctuation at different times of the day remained unchanged. The urinary excretion of 17-oxogenic steroids was lower (P less than 0.01) during treatment than before or after treatment with both contraceptive combinations. The metyrapone test showed normal adrenal responsiveness during the treatment cycles. The urinary excretion of free cortisol was unchanged when desogestrel + EE was used, but increased (P less than 0.01) during treatment with levonorgestrel + EE. However, even then, the urinary free cortisol was within the normal range of the population. All the test results of hormone determinations normalized soon after finishing the contraceptive treatments. It is suggested that the abnormalities seen were due to an increased serum binding capacity of cortisol induced by EE and not a sign of pathological changes in adrenal function. No major differences in the biological effects of the two combinations tested were seen.     

Growth hormone deficiency as the only identifiable cause for primary amenorrhea

Background: There is much evidence that growth hormone plays an important role in the development and function of the reproductive system of both males and females. Growth hormone exerts its effects on the ovarian follicular cycle directly or by local production of insulin-like growth factor 1 (IGF-1). It is known that growth hormone deficiency during childhood may delay pubertal development, but there is limited data about primary amenorrhea in GH-deficient girls with sufficient stimulated gonadotropin levels.Methods: Case series.Results: In the evaluation of primary amenorrhea and delayed puberty, 3 cases of adolescent females aged 17-19 years were identified as isolated GH-deficiency. Among the 3 patients, 2 had history of intracranial surgery due to hydrocephalus (shunt operation) or prolactin-secreting pituitary macro-adenoma (transphenoidal surgery, one year before). 17-year-old patient with shunted hydrocephalus and 19-year-old patient with primary amenorrhea showed short statue (< 5%) and delayed bone maturation. The patient undertaken transphenoidal surgery for prolactinoma showed normal height and bone maturation. There was no familial history of delayed puberty. On physical examination, 3 patients showed variable degree of breast development from Tanner stage II to IV without sex-steroid replacement. In sella MRI, small pituitary gland were identified in 2 patients with short statue and delayed bone maturation. All of the 3 patients underwent combined pituitary function test. After insulin-induced hypoglycemia, peak growth hormone levels of the 3 patients were 0.08, 1.4 and 1.4 ng/ml and were compatible with growth hormone deficiency. Peak LH after intravenous gonadrelin (FACTREL) were 19.0 to 56.1 mIU/ml and LH % responses were 217 to 1100% and were hence defined as not being gonadotropin deficiency. Other anterior pituitary functions were normal in all of the 3 patients.Conclusions: We found isolated growth hormone deficiency as the only identifiable cause for primary amenorrhea in three patients with sufficient gonadotropins secretion. These findings suggest a complementary role of GH to gonadotropins in the occurrence of menarche.     

The effect of a single course of antenatal corticosteroids on maternal adrenal function at term.

OBJECTIVE: To determine if one course of antenatal corticosteroids at 32 weeks produces maternal adrenal suppression at term. METHODS: The adrenocorticotropic hormone (ACTH) stimulation test was administered at 38 weeks to 11 pregnant women who had received a single course of antenatal betamethasone prior to 33 weeks and to six control subjects. RESULTS: There was no difference in basal cortisol levels (mean+/-standard deviation) between the two groups: 41.6+/-6.9 microg/dl for controls versus 36.0+/-7.8 microg/dl for the steroid group, p=0.16. Peak cortisol levels at 45 min following ACTH stimulation were not different: 61.6+/-3.5 microg/dl for controls versus 55.0+/-2.6 microg/dl for the steroid group, p=0.16. The power of the study to detect a statistical difference in the observed peak cortisol levels was greater than 95%. None of the study subjects had laboratory criteria or clinical signs of adrenal suppression. CONCLUSIONS: A single course of betamethasone for women at risk for preterm delivery does not produce adrenal insufficiency at term and stress dose steroids are not recommended.     

Metformin administration modulates neurosteroids secretion in non-obese amenorrhoic patients with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disease that is observed frequently to be related to increased insulin resistance. The use of insulin-sensitizer compounds, such as metformin, permits great improvement of such metabolic abnormality and the restoration of normal ovarian function. Metformin administration reduces insulin resistance and androgen production both from the ovary and adrenal gland. AIM: On this basis we aimed to evaluate a group of non-obese amenorrheic PCOS patients before and after 6 months of metformin administration (500 mg per os twice daily) to better understand what changes might be induced by metformin on adrenal and ovarian function and in terms of temporal coupling of the pulsatile profiles of luteinizing hormone (LH), cortisol and allopregnanolone, the latter representative of the neurosteroid family. METHOD: A group of non-obese PCOS patients (n = 8) was enrolled after informed consent and underwent to a pulsatility study for LH, cortisol and allopregnanolone, and an oral glucose tolerance test before and on day 7 of the first menstrual cycle occurring after the 5th month of treatment. RESULTS: Plasma androgen levels were decreased significantly by metformin treatment, as were plasma LH and allopregnanolone levels and insulin resistance. Metformin administration decreased LH pulse amplitude but not pulse frequency. On the contrary, cortisol and allopregnanolone showed a significant change in pulse frequency. When temporal coupling was tested between pulsatile profiles of LH or cortisol with allopregnanolone, cortisol pulses were temporally coupled to allopreganolone peaks both before and under metformin administration while LH pulses were temporally coupled to allopreganolone secretory peaks only under metformin treatment. CONCLUSIONS: Our data demonstrate that metformin administration modulates LH secretion as well as cortisol and allopregnanolone pulsatile release. In addition, the results demonstrate that adrenal and ovarian steroidogenic activity is greatly modulated by any change in insulin sensitivity.     

Endocrine evaluation in a patient with MURCS association and ovarian agenesis

A new case of Mullerian duct aplasia, renal aplasia, and cervicothoracic somite dysplasia (MURCS association) in a 16-yr-old female patient is reported. In addition, agenesis of the right ovary plus hypoplasia of the right craniofacial bones were also present. Dynamic tests of anterior pituitary reserve (LH-RH, TRH and hypoglycemia) showed normal responsiveness of this gland in terms of LH, FSH, TSH, prolactin and growth hormone secretion, whilst a subnormal plasma cortisol response to hypoglycemia and exogenous ACTH (in the presence of unilateral adrenal agenesis) was found. Functional integrity of the hypothalamic-pituitary-ovarian axis was also documented. The presence of two additional and previously unreported congenital anomalies in this patient with MURCS association underlines the wide spectrum of the syndrome.