Type A-insulin resistance with lipopexia on extremities: a case report.

We present the unusual case of a 17-year-old female with insulin-resistant diabetes, acanthosis nigricans, hirsutism, amenorrhea, dental dysplasia and lipopexia on the extremities. She had been diagnosed as having border line diabetes with hyperinsulinemia at age 12 when she was not obese and diabetes mellitus at age 13. On admission, she was obese and had lipopexia only on the extremities. The presence of hyperinsulinemia and poor response to exogenous insulin suggested severe insulin resistance. Insulin binding to transformed B-lymphoblasts derived from her was extremely low compared to the normal control, showing decreased receptor affinity. Her parents and sister exhibited hypersecretion of insulin in response to a 75 g oral glucose tolerance test. Her mother was diabetic, and her father and sister had border line diabetes, whereas her brother had a normal response. These findings support strongly the diagnosis of a type A syndrome with severe insulin resistance associated with lipopexia on the extremities. A genetic defect in the insulin receptor gene may be responsible.     

Idiopathic premature ovarian failure in 63 young women

BACKGROUND: Premature ovarian failure (POF) in adolescents is defined as primary or secondary amenorrhea associated with high follicle-stimulating hormone (FSH) levels. In normal 46,XX patients, its etiology is most often unknown. We have evaluated the clinical, hormonal and ovarian phenotypes in patients with a normal karyotype who were diagnosed with POF before the age of 18. METHODS: Sixty-three patients were included in this retrospective study. RESULTS: The mean patient age was 20.4 years. The patients presented with three clinical patterns: lack of pubertal development (n = 23), primary amenorrhea with interrupted puberty (n = 18), and secondary amenorrhea with normal puberty (n = 22). Ten patients had a familial history of POF and 6 presented with hypothyroidism. The FSH, estradiol and inhibin B levels were not statistically different in the three clinical groups. Fifty percent of the patients presented small ovaries (length <2 cm) at ultrasonography. The presence of follicles was found at histology in only 7 of the 27 patients who underwent an ovarian biopsy. CONCLUSION: 46,XX patients presenting with early POF rarely presented a specific, identifiable disorder. We discuss the clinical management and different diagnosis strategies to improve our current knowledge of this syndrome.     

Assessing reproductive status in orang-utans by using urinary estrone

The aim of this work was to compare normal menstrual cycle patterns of urinary estrone excretion in orang-utans with those of an orang-utan in her late 40s, an orang-utan before and after rehabilitation for anorexia, and an orang-utan during prolonged lactation. A detailed menstrual and sexual activity record was kept for each orang-utan subject. Urine samples for estrone radioimmunoassay were collected daily for two cycles whenever possible. “Mawas,” in her late 40s, was monitored for two cycles in each of 3 successive years. While the normal pattern of estrone excretion was initially seen, some of the later cycles were shorter and appeared to lack the large luteal-phase peak. “Puspa,” anorexic and amenorrhoeic at the age of 9½ years, had very low urinary estrone concentrations. After rehabilitation, followed by a late menarche, she had regular menstrual cycles with a normal estrone excretion pattern. She gave birth to a normal infant in 1990. “Puteri,” who had been lactating for 2 years, had consistently low estrone concentrations during an 8-week monitoring period, with no evidence of cyclic variation in estrone excretion. Daily urinary estrone measurements, together with observation, were found to be useful in assessing the reproductive status of orangutans.     

Cytogenetic investigation of 103 patients with primary or secondary amenorrhea

Cytogenetic investigations were carried out on 103 women presenting with either primary (n = 88) or secondary (n = 15) amenorrhea. A sex chromosome anomaly was found in 26% and 33% of these patients, respectively. Other studies on women with primary amenorrhea have found a similar or even higher percentage of patients with an abnormal karyotype. It is therefore suggested that all women with absence of menstruation after the age of 16 years should be investigated cytogenetically. The surprisingly high percentage of pathological karyotypes among the secondary amenorrhea group does indicate that sex chromosome anomalies cannot be ruled out in women who have had apparently normal ovarian function for at least some time, and therefore more patients from this group should be selected for chromosome analysis.     

Assessment of care of children with sickle cell disease: implications for neonatal screening programmes.

OBJECTIVE--To assess the quality of care provided by hospitals for young children with sickle cell disease. DESIGN--Retrospective survey. SETTING--Teaching hospital in London. PATIENTS--31 Children (mean age 4 years 4 months, range 4 months to 7 years 5 months) born with sickle cell disease between 1978 and 1985 identified from Hospital Activity Analysis data, an outpatient diagnostic register, and registers of the haematology department. Eight had been diagnosed on neonatal screening and at least four of these had not been followed up. MAIN OUTCOME MEASURES--Aspects of quality of outpatient care (blood testing, clinic attendance, and prophylactic drug treatment) and family care (adequate support and carers'' knowledge about the disease) as assessed by reviewing the notes and administering a semistructured questionnaire to the carers, in relation to a devised list of standards deemed necessary to ensure achievement of the aims of screening. RESULTS--There were 93 outpatient attendances during the previous 12 months, but 13 children had not attended at least every six months and four not at all for more than a year. Only eight children had had three of the blood tests considered to be necessary for good care; three had had none. Prophylactic treatment with penicillin and folic acid was erratic; three children with sickle cell anaemia were not receiving regular prophylactic penicillin. IMPLICATION--Diagnosis of sickle cell disease on neonatal screening must be linked with follow up to ensure optimal management.     

Aetiological approach of female reproductive physiology in lactational amenorrhoea.

The duration of postpartum amenorrhea and return of ovulation varies on an individual and population basis. In 1980, in Senegal, the relationship of chronic malnutrition and female fertility was investigated for 2 years. The stability of the female body regarding weight and arm circumference despite a heavy annual workload was a surprising finding. The mean female body mass index was higher for lactating women in amenorrhea than required for restoring menstruation in European women. The mean duration of postpartum amenorrhea was 18.2 +or- .6 months. The difference between those who resumed menstruation (20.9 +or- .9 months) and who still had amenorrhea (25.4 +or- 2.2 months) was significant. The duration of breast feeding determined the duration of amenorrhea. Studies have found a link between ovarian dysfunction and women in harsh third world environments and sportswomen under intensive training with both showing irregular menstruation and amenorrhea. Long duration of cycles in New Guinean women, high amount of anovulation in Zairian forest women, and suppression of testosterone and estradiol levels in hunter-gatherers were found. In affluent Europeans and urbanized women in developing countries postpartum amenorrhea dropped drastically. Long distance runners are often vegetarians with low calorie consumption and with a high degree of menstrual trouble owing to low body fat and weight-for-height. The role of beta-endorphins in the hypothalamic blockade of the gonadotropin releasing hormone pulse generator and high stress or physical training is proven. The functioning of the hypothalamo-pituitary-ovarian axis can be hurt by intensive training. Short-term fasting also suppressed the pulsatile luteinizing hormone and testosterone secretion. The protocol and methodology of an etiological study is outlined regarding the factors of this hypothesis on amenorrhea.     

Influence of number of gilts per pen on estrous traits in confinement-reared gilts

One hundred forty-four Yorkshire (Y) x Landrace (L) and Chester White (CW) x Large White (LW) reciprocal cross gilts (Trial I) and 147 CW:LW x Y:L reciprocal cross gilts (Trial II), 4.5 to 5 months old, were penned in groups of 3, 9, 17 or 27 (1.1 m(2)/gilt). Estrus was checked daily from seven to nine months of age. Reproductive tracts of all noncyclic gilts were examined at nine months of age. Between seven and nine months of age, 12% to 16% fewer (P<0.05) gilts in pens of three had regular estrous cycles, and the percentage of gilts with regular estrous cycles did not differ with more (9, 17 or 27) gilts/pen. At nine months of age, 56.9% of the gilts penned in groups of three were cyclic as compared to 78%, 80.4% and 80.7% of the gilts penned in groups of 9, 17 and 27, respectively. In Trial I, more (P<0.05) CW x LW reciprocal cross gilts were cyclic compared to Y x L reciprocal cross gilts at nine months of age. The CW x LW group had fewer behaviorally anestrous gilts and more cyclic gilts, regardless of the number of gilts/pen. The social cues involved in the process of sexual development of gilts remain undefined, but extremes in the number of gilts/pen should be avoided.     

Gradual progress of ACTH deficiency in a child with panhypopituitarism associated with pituitary stalk transection.

We present here a 13-year-old male with hypopituitarism which accompanied an insidious and gradual progress of ACTH deficiency. ACTH deficiency finally led to an overt crisis of adrenal insufficiency at the age of 12 years and 7 months. This patient is unique because the insidious and gradual progress has been proved by not only the laboratory results but also the clinical course for over 13 years. The cause of panhypopituitarism including ACTH deficiency is thought to have existed before or at the delivery because of the stalk transection seen on the magnetic resonance image (MRI). At the crisis, his laboratory results suggested that he had secondary adrenal insufficiency, whereas he showed normal adrenal function proved by the insulin tolerance test (ITT) at the age of 4 years. Abrupt crisis of secondary adrenal insufficiency developed at the age of 12 years, although he had been well until the crisis.     

Fluctuations in peripheral serum testosterone levels within a day, with age and by sexual stimulation in male beagle dogs bred indoors

Fluctuations in serum levels of testosterone (T) within a day, both with age and as a result of sexual stimulation, were examined in male beagle dogs. Eighty male dogs aged between 3 months and 16 years and bred in our laboratory were used under strictly controlled breeding conditions (temperature: 22 +/- 1 degree C, relative humidity: 55 +/- 5%, lighting time: 8:00 a.m.-8:00 p.m.). The level of T was measured by an RIA method. In order to examine the fluctuation in T level within a day, blood samples were obtained at 0:00, 6:00, 12:00 and 18:00 in each of five dogs aged 1.7 and 2.1 years. T levels fluctuated with a regular pattern that was lowest at 12:00, and increased to a peak at 18:00-6:00, thereafter decreasing until 12:00. In order to examine the change in T level with age, blood samples were obtained at 9:00, 12:00 and 16:00 from 70 dogs aged between 3 months and 16 years. The regular diurnal pattern of T level was usually seen, and the levels at 12:00 were always low and did not fluctuate at any age except for 6 months, and 13, 14 and 16 years. The T level at 9:00 increased to reach a peak at 4 years, whereas that at 16:00 did so at 2 years. T levels at 9:00 were significantly higher at 4-12 and 14 years than at 3 months, and were higher at 4 years than at 9 months.(ABSTRACT TRUNCATED AT 250 WORDS)     

Partial 7q Isochromosome in Bone Marrow Following Treatment of Hodgkin's Disease

We report on a 29-year-old female followed for relapsed Hodgkin's disease. She had been diagnosed with Hodgkin's disease at 20 years of age and had been treated with chemotherapy. She had been in remission for six years when she relapsed, at which time she received chemotherapy for bone marrow transplant (BMT). After failure of BMT, she received additional chemotherapies with growth factors and radiation treatment. A bone marrow biopsy showed moderate hypercellularity with erythroid hyperplasia, but the karyotype had an abnormal clone containing an isochromosome derived from a 7q22 deletion.     

Management of women at increased risk for breast cancer: preliminary results from a new program

OBJECTIVE: To examine the characteristics of malignant tumours that develop in women undergoing surveillance for increased risk for breast cancer and to identify presentation patterns in order to determine the respective roles of mammography, clinical breast examination (CBE) and breast self-examination (BSE). SETTING: Breast Diagnostic Clinic and Familial Breast Cancer Clinic at Toronto-Sunnybrook Regional Cancer Centre. PARTICIPANTS: A total of 1044 women evaluated for breast cancer risk from Oct. 1, 1990, to Dec. 31, 1996, of whom 381 were categorized as being at high risk, 204 as being at moderate risk, 401 as being at slightly increased risk and 58 as being at no appreciably increased risk. PROGRAM COMPONENTS: Comprehensive review and discussion of risk factors, clinical assessment, surveillance recommendations that include mammography, CBE and BSE, genetics consultation (Familial Breast Cancer Clinic) and psychosocial support. Data are captured prospectively, updated at each visit and audited every 3 to 6 months. PROGRAM OUTCOMES: During the study period breast cancer was diagnosed in 24 patients, 12 in the high-risk group, 4 in the moderate-risk group and 8 in the group at slightly increased risk. The mean age at diagnosis was 47 (range 32 to 82) years. Ten cases of cancer were diagnosed during surveillance (incident cancer), 5 in women under age 50. The mean length of time from initial assessment to diagnosis was 28.6 (range 12 to 51) months. Of the 24 women, 17 reported a family history of breast cancer. The mean age at diagnosis in this cohort was 45.5 years, and the diagnosis was made under age 50 in 10 patients (59%). The mean earliest age at which breast cancer was diagnosed in a family member was 42.5 years. CONCLUSIONS: These preliminary results suggest that surveillance of women at increased risk for breast cancer may be useful in detecting disease at an early stage. The regular performance of mammography, CBE and BSE appears necessary to achieve these results.     

Reproductive function in aged female chimpanzees.

Reproductive function was evaluated in ten female chimpanzees (Pan troglodytes) aged 35-48 years. Forty-eight years is the longevity record for the chimpanzee. Data on cycle frequency and duration was available for seven animals. Most were cycling regularly until death, and all had experienced at least one menstrual cycle within one year of death. After exclusion of periods when the animals were pregnant or in postpartum amenorrhea, the mean cycle frequency (+/- standard error)/year was 9.54 +/- 0.20 in seven animals aged 15-25 (432 cycles analyzed) compared to 8.6 +/- 0.76 in the same animals at age 35 + years (405 cycles analyzed); this effect approached significance (p = 0.072, Mann-Whitney U-test). Cycle length of 16 cycles in each of seven animals aged 15-25 was 32.23 +/- 0.38 days. The same animals when aged over 35 had mean cycle lengths of 35.59 +/- 0.73. This difference was not significant, although cycle lengths clearly increased with age in some individual animals. In five aged animals for which mating data was available, appropriate exposure to a male occurred in 52 cycles, but only two pregnancies occurred; one pregnancy resulted in a live birth at age 38, the other in a stillbirth at age 40. This conception rate was 3.85% compared with 20% in the same animals aged 15-25. These data suggest greatly reduced fertility after age 35, although menstrual cycle frequency remained high. The persistence of menstrual cyclicity until death, which occurred due to natural causes at latest in the fifth decade, is in striking contrast to the human female in which menopause occurs in the fifth decade and death is often postponed for several more decades.     

Positive Prolactin Response to Bromocriptine in 2 Patients with Cabergoline-Resistant Prolactinomas

ObjectiveTo describe a positive prolactin response to bromocriptine treatment in 2 patients with cabergolineresistant prolactinomas.MethodsWe report the patients’ clinical presentations, laboratory test results, imaging findings, and clinical courses.ResultsPatient 1 had a 5-mm pituitary microadenoma that was initially diagnosed at age 30 years. After initial diagnosis, she was treated with transvaginal bromocriptine for 9 years and then subsequently went untreated for 2 years. After developing symptoms of amenorrhea, decreased libido, and hyperprolactinemia, oral cabergoline, 0.5 mg twice weekly, was initiated. Her prolactin concentration remained elevated at 80 ng/mL while taking cabergoline. Her prolactin concentration decreased to 13 ng/mL after her regimen was switched to bromocriptine, 5 mg daily. Patient 2 had a 17-mm pituitary macroadenoma that was initially diagnosed at age 15 years. Oral cabergoline was started at 0.5 mg twice weekly and increased to 1 mg 3 times weekly when prolactin levels continued to rise to 340 ng/mL over 18 months. After visual field defects developed, transsphenoidal surgery was performed. One year after surgery, magnetic resonance imaging showed a 6-to 7-mm pituitary adenoma, and there was a gradual rise in serum prolactin. Her serum prolactin concentration continued to rise to 212 ng/mL with increasing tumor size over 3 years. Cabergoline was discontinued and oral bromocriptine was initiated at a dosage of 10 mg daily. After 4.5 months of bromocriptine therapy, her serum prolactin concentration decreased to 133 ng/mL. However, after 2 months, the macroadenoma continued to increase in size and a visual field defect developed, so another transsphenoidal operation was performed.ConclusionsAlthough cabergoline is generally preferred to bromocriptine for the treatment of patients with prolactinomas because of its better tolerance profile and greater effectiveness, in patients with cabergoline-resistant prolactinomas, a bromocriptine trial should be considered a safe, relatively inexpensive, and well-tolerated alternative. (Endocr Pract. 2011;17:e55-e58)     

Influence of the Male Axillary Extracts on Regulation of Menstrual Cycles in Women

The effect of male axillary extract on the length and regularity of the menstrual cycle in women was studied in a long-term experiment (9 months). The male secret extract had no statistically significant influence on the menstrual cycle duration in the reproductive-age women (21–45 years) with normal (26–32 days) and regular cycles or in women with abnormally short (<26 days) cycles. In the group of the reproductive-age women with irregular and abnormally long (>32 days) cycles, as well as in the group of the premenopauseage women (46–51 years) with irregular cycles, the secret extract caused a significant shortening of the menstrual cycle as compared to the control. The effect was preserved for at least two months after the exposure completed.     

Postpartum lactational amenorrhoea as a means of family planning in the Sudan: a study of 500 cases

The lactational histories of 500 Sudanese women were studied retrospectively to examine postpartum lactational amenorrhea as a method of family planning. Particular attention was given to the factors affecting postpartum lactational amenorrhea, including supplementary feeding and the use of modern contraceptive methods. Breast-feeding was overwhelmingly practised (90%) among this sample, which was roughly representative of the Sudanese population as a whole. The prevalence of amenorrhea among this group of lactating women was quite high (73%). Duration of lactational amenorrhea ranged from 2 to 36 months with a median of 12 months. Introduction of supplementary feeding had little effect on lactational amenorrhea up to the 9th month of breastfeeding. Beyond the 12th month of breastfeeding, lactational amenorrhea was significantly prolonged by postponing the introduction of supplementary feeding until the 4th month or later. Ovulation, and hence conception, during lactational amenorrhea was unpredictable. It occurred as early as the 3rd or as late as the 36th month postpartum. Conceptions interrupting lactational amenorrhea soon after delivery (3-9 months) were more frequent among primiparous women. The failure rate of lactational amenorrhea as a contraceptive was 8.4%. Though extremely high compared to that of the pill, lactational amenorrhea was more useful as a fertility control mechanism because, in this study, a high proportion of women initiated pill use, but soon discontinued it because of side effects. Modern contraceptive practice was not prevalent. Amenorrheic mothers accepted the pill after the 6th month postpartum (41%, compared to lactating mothers whose menses had returned who started much earlier. 49% of the women studied relied completely on the protection of lactational amenorrhea. 57% of all lactating women who used the combined pill reported a reduction in milk production. Knowledge of modern contraception was poor and incorrect in many cases, leading to several policy implications, including usage of sterilization.     

Metformin-Responsive Classic Salt-Losing Congenita L Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency: a Case Report

ObjectiveTo study the effect of adding metformin to standard steroid replacement therapy in a patient with classic salt-losing congenital adrenal hyperplasia due to 21- hydroxylase deficiency with suboptimal biochemical and clinical control.MethodsWe present the clinical and laboratory findings before and after the addition of metformin to the therapeutic regimen of the study patient.ResultsA 17-year-old girl had been diagnosed as a neonate with classic salt-losing congenital adrenal hyperplasia caused by 21-hydroxylase deficiency (CYP21A2 deficiency). She was treated with hydrocortisone, 20 mg in the morning and 10 mg at bedtime, and fludrocortisone, 50 mcg daily. While on steroid replacement, she maintained normal serum electrolytes, glucose, blood pressure, and external genitalia, but she continued to express clinical features of obesity, hirsutism, amenorrhea, and acanthosis nigricans. Elevated laboratory measurements included the following: fasting 17-hydroxyprogesterone, 3410 ng/dL; total testosterone, 326 ng/dL; and androstenedione, 390 ng/dL. She was initiated on metformin, 500 mg twice daily after meals. After 3 months, the patient lost 2 kg, amenorrhea resolved, 17-hydroxyprogesterone decreased to 1539 ng/dL, total testosterone decreased to 163 ng/dL, and androstenedione levels remained unchanged.ConclusionsMetformin, an agent known to reduce insulin resistance, further suppressed the 17-hydroxyprogesterone concentration in a patient with classic congenital adrenal hyperplasia on steroid replacement therapy. Metformin may improve clinical and biochemical outcomes in classic congenital adrenal hyperplasia without the risk of iatrogenic Cushing syndrome. (Endocr Pract. 2008;14:889-891)     

Effects of hGRF treatment of a patient with hGRF deficiency

A 12-year old girl was admitted to our hospital for evaluation of her short stature. Her height was below -3.5 SD of the mean height for her age. She was diagnosed as having craniopharyngioma and treated surgically. Thereafter she was treated with thyroxine and hydrocortisone. One and a half years later, she revisited our hospital for treatment of short stature. Her plasma GH did not respond to insulin-induced hypoglycemia but increased after hGRF-44 administration, indicating hGRF deficiency. hGRF was therefore administered at a dosage of 100 micrograms twice a day subcutaneously for three months. Her height increased 1.6 cm during treatment, which corresponded to a height increase of 6.4 cm/year. These findings indicate that hGRF treatment stimulates height increase in patients with GRF deficiency. For complete evaluation of hGRF therapy, further studies will be required.     

Children diagnosed with diabetes during infancy have unique clinical characteristics

OBJECTIVE: Characterizing clinical and biochemical features of children diagnosed with diabetes mellitus between the ages of 6-24 months. DESIGN AND METHODS: Medical records of 42 children diagnosed with diabetes mellitus at age of 6-24 months were reviewed for gender, ethnic origin, family medical history, clinical and biochemical features at onset of diabetes compared with 60 diabetic patients diagnosed at age 5-16 years. RESULTS: Children diagnosed at 6-24 months had at onset more symptoms of apathy, restlessness, hyperglycemia during acute illness and a lower rate of remission than those diagnosed at older age (p < 0.001), significantly more episodes of diabetic ketoacidosis (83% vs. 40%, p < 0.001), lower HbA1c levels (mean 11.6 +/- 3.4 vs. 13.75 +/- 3.4%, p < 0.05) and a higher rate of celiac disease (12% vs. 3%, p = 0.046). There were no significant differences as to other autoimmune diseases. CONCLUSIONS: Patients with diabetes presenting at 6-24 months might be associated with a different clinical pattern and higher rate of celiac disease than diabetes presenting later in life. Understanding the nature and course of diabetes in this age group is crucial for planning interventional and preventive programs.