Management of hypoparathyroidism in pregnancy and lactation - A report of 10 cases.

INTRODUCTION: Hypoparathyroidism in pregnancy is rare, but important, as it is associated with maternal morbidity and foetal loss. There are limited case reports and no established management guidelines. Optimal maintenance of calcium levels during pregnancy is required to minimise the risk of related complications. This study aims to identify causes and examine outcomes of hypoparathyroidism in pregnancy in a cohort of women delivering at a large referral centre. DESIGN AND METHOD: The Monash Health maternity service database captures pregnancy and birthing outcomes in over 9000 women each year. We audited this database between 2000 and 2014 to examine the clinical course, treatment and outcomes of pregnant women with hypoparathyroidism. RESULTS: We identified 10 pregnancies from 6 women with pre-existing hypoparathyroidism secondary to idiopathic hypoparathyroidism (n = 3), autosomal dominant branchial arch disorder with hypoparathyroidism (n = 3) and autosomal dominant hypocalcaemia (n = 1), surgery for thyroid cancer (n = 2) and Graves' disease (n = 1). Maternal calcium levels were monitored through pregnancy and management adjusted to maintain normocalcaemia. One woman was delivered by caesarean section at 34 weeks' gestation because of intrauterine growth restriction, and oligohydramnios complicated two other pregnancies. The postpartum period was complicated by severe hypercalcaemia in one woman and by symptomatic, labile serum calcium levels during lactation in another woman, requiring close monitoring over a 6 month period. CONCLUSION: Although rare, hypoparathyroidism in pregnancy poses a management challenge for clinicians, and co-ordinated care is required by obstetricians and endocrinologists to ensure optimal outcomes for both mother and baby. Continued monitoring of maternal calcium levels during lactation and weaning is essential to avoid the potential complications of either hypercalcaemia or hypocalcaemia.

Prolonged hypocalcemia following denosumab therapy in metastatic hormone refractory prostate cancer.

Prostate cancer is a leading cause of cancer death, frequently associated with widespread bone metastases. We report two cases of hypocalcemia following the first dose of denosumab in metastatic hormone refractory prostate cancer, the first case requiring 26 days of intravenous calcium therapy. This is the first report of prolonged hypocalcemia following denosumab in a patient with normal renal function.

Chemical constituents and anticancer effects of the essential oil from leaves of Xylopia laevigata.

Xylopia laevigata, popularly known as "meiú" and "pindaíba", is a medicinal plant used in the folk medicine of the Brazilian Northeast for several purposes. The chemical constituents of the essential oil from leaves of X. laevigata, collected from wild plants growing at three different sites of the remaining Atlantic forest in Sergipe State (Brazilian Northeast), were analyzed by GC/FID and GC/MS. The effect of the essential oil samples was assessed on tumor cells in culture, as well on tumor growth in vivo. All samples of the essential oil were dominated by sesquiterpene constituents. A total of 44 compounds were identified and quantified. Although some small differences were observed in the chemical composition, the presence of γ-muurolene (0.60-17.99%), δ-cadinene (1.15-13.45%), germacrene B (3.22-7.31%), α-copaene (3.33-5.98%), germacrene D (9.09-60.44%), bicyclogermacrene (7.00-14.63%), and (E)-caryophyllene (5.43-7.98%) were verified as major constituents in all samples of the essential oil. In the in vitro cytotoxic study, the essential oil displayed cytotoxicity to all tumor cell lines tested, with the different samples displaying a similar profile; however, they were not hemolytic or genotoxic. In the in vivo antitumor study, tumor growth inhibition rates were 37.3-42.5%. The treatment with the essential oil did not significantly affect body weight, macroscopy of the organs, or blood leukocyte counts. In conclusion, the essential oil from the leaves of X. laevigata is chemically characterized by the presence of γ-muurolene, δ-cadinene, germacrene B, α-copaene, germacrene D, bicyclogermacrene, and (E)-caryophyllene as major constituents and possesses significant in vitro and in vivo anticancer potential.

In vitro and in vivo antitumor effects of the essential oil from the leaves of Guatteria friesiana.

Guatteria friesiana (W. A. Rodrigues) Erkens & Maas (synonym Guatteriopsis friesiana W. A. Rodrigues), popularly known as "envireira", is a medicinal plant found in the Brazilian and Colombian Amazon basin that is used in traditional medicine for various purposes. Recent studies on this species have demonstrated antimicrobial activity. In this study, the antitumor activity of the essential oil from the leaves of G. friesiana (EOGF) and its main components ( α-, ß-, and γ-eudesmol) were determined using experimental models. In the in vitro study, EOGF and its components α-, ß-, and γ-eudesmol displayed cytotoxicity against tumor cell lines, showing IC50 values in the range of 1.7 to 9.4 µg/mL in the HCT-8 and HL-60 cell lines for EOGF, 5.7 to 19.4 µg/mL in the HL-60 and MDA-MB-435 cell lines for α-eudesmol, 24.1 to > 25 µg/mL in the SF-295 and MDA-MB-435 cell lines for ß-eudesmol, and 7.1 to 20.6 µg/mL in the SF-295 and MDA-MB-435 cell lines for γ-eudesmol, respectively. In the in vivo study, the antitumor effect of EOGF was evaluated in mice inoculated with sarcoma 180 tumor cells. Tumor growth inhibition rates were 43.4-54.2 % and 6.6-42.8 % for the EOGF treatment by intraperitoneal (50 and 100 mg/kg/day) and oral (100 and 200 mg/kg/day) administration, respectively. The treatment with EOGF did not significantly affect body mass, macroscopy of the organs, or blood leukocyte counts. Based on these results, we can conclude that EOGF possesses significant antitumor activity and has only low systemic toxicity. These effects could be assigned to its components α-, ß-, and γ-eudesmol.

Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in nonobese aging men.

BACKGROUND: Trials of testosterone therapy in aging men have demonstrated increases in fat-free mass (FFM) and skeletal muscle and decreases in fat mass (FM) but have not reported the impact of baseline body composition. OBJECTIVE: The objective of the study was to determine the effect, in nonobese aging men with symptoms of androgen deficiency and low-normal serum testosterone levels, of testosterone therapy on total and regional body composition and hormonal and metabolic indices. METHODS: Sixty healthy but symptomatic, nonobese men aged 55 yr or older with total testosterone (TT) levels less than 15 nm were randomized to transdermal testosterone patches or placebo for 52 wk. Body composition, by dual-energy x-ray absorptiometry (FM, FFM, skeletal muscle) and magnetic resonance imaging (abdominal sc and visceral adipose tissue, thigh skeletal muscle, and intermuscular fat) and hormonal and metabolic parameters were measured at wk 0 and 52. RESULTS: Serum TT increased by 30% (P = 0.01), and LH decreased by 50% (P < 0.001). Relative to placebo, total body FFM (P = 0.03) and skeletal muscle (P = 0.008) were increased and thigh skeletal muscle loss was prevented (P = 0.045) with testosterone therapy and visceral fat accumulation decreased (P = 0.001) without change in total body or abdominal sc FM; change in visceral fat was correlated with change in TT levels (r2 = 0.36; P = 0.014). There was a trend to increasing total and low-density lipoprotein cholesterol with placebo. CONCLUSION: Testosterone therapy, relative to placebo, selectively lessened visceral fat accumulation without change in total body FM and increased total body FFM and total body and thigh skeletal muscle mass. Further studies are needed to determine the impact of these body compositional changes on markers of metabolic and cardiovascular risk.

Stereotactic radiosurgery XVI: a treatment for previously irradiated pituitary adenomas.

We report the use of stereotactic radiosurgery delivered through an adapted linear accelerator [stereotactic multiple arc radiation therapy (SMART)] for pituitary adenomas not cured by conventional therapy. All 21 patients had undergone conventional radiotherapy (45-50 Gy); 18 had also undergone prior surgery. This cohort comprised 13 patients with somatotrope adenomas, four with corticotrope adenomas, one with a lactotrope adenoma, and three with nonfunctioning pituitary adenomas (median follow-up: 33 months, range: 3-72 months). SMART has proven effective, safe, and rapidly acting. We observed an accelerated reduction in GH and IGF-I levels in acromegaly, with normalization of GH and IGF-I levels in 58%. Mean GH fell from 21.1 mU/liter to 7.9 mU/liter (7 ng/ml to 2.6 ng/ml, P < 0.01, median 25 months) faster than our predicted fall to 50% at 2 yr with conventional radiotherapy. Mean IGF-I fell from 624 ng/ml to 384 ng/ml (P < 0.001). Tumor growth was controlled in two of three nonfunctioning pituitary adenomas, and three of four corticotrope adenomas. There were no adverse effects from SMART. Notably there have been no visual sequelae or further loss of anterior pituitary function in this heavily pretreated group. Our data indicate that SMART is an effective complementary therapy for pituitary adenomas that have displayed a suboptimal response to conventional therapy including external irradiation.

Pituitary chondrosarcoma: an unusual cause of a sellar mass presenting as a pituitary adenoma.

A 37-yr-old woman with clinical, endocrinological, and radiological features suggestive of a nonfunctioning pituitary tumor was found to have a chondrosarcoma of the pituitary sella. The bony structures around the sella were relatively uninvolved, other than showing minor erosion of the left side of the dorsum and the posterior wall of the sphenoid sinus. After partial resection of the tumor by the transsphenoidal route the patient received postoperative radiosurgery by a linear accelerator, stereotactic multiarc radiotherapy. Subsequent follow-up revealed reduction of the residual tumor. This case demonstrates that a chondrosarcoma may apparently arise directly from the pituitary fossa and suggests the efficacy of stereotactic radiosurgery, at least in the medium term. The origin, areas of involvement, management, and long-term prognosis of these rare tumors are reviewed.

Concurrent secretion of aldosterone and cortisol from an adrenal adenoma - value of MRI in diagnosis.

A 43-year-old female with a 24-years history of hypertension presented for further investigation and management of primary hyperaldosternoism. Postural studies were not conclusive and magnetic resonance (MR) imaging demonstrated a 27 x 18 mm lesion of the right adrenal gland which showed no signal loss during in and out of phase imaging. Although these appearances were considered to be atypical of those seen on MR in patients with aldosterone producing adrenal adenomas the patient underwent an adrenalectomy with removal of a 3 x 3 x 2 cm right adrenal mass. Post-operatively she became hypotensive and a 0900 hours serum cortisol was undetectable (< 50 nmol/l), consistent with adrenal insufficiency. Following the administration of hydrocortisone there was normalization of the blood pressure and subsequent adrenal stimulation tests confirmed the presence of functioning adrenal tissue albeit with an inadequate response. Cortisol measurement from preoperative samples revealed loss of normal diurnal rhythm whereas DHEAS levels both pre and postoperatively were undetectable, consistent with ACTH supression resulting from autonomous cortisol secretion in addition to aldosterone. Concurrent secretion of cortisol should always be considered in Conn's adenomas particularly when atypical radiological features are present.

Acknowledging alcohol problems. The use of a visual analogue scale to measure denial.

Despite the frequent mention of denial in the alcohol treatment literature, there appears to be no consensus about its measurement. At its most basic, an operational definition of the term should contain the notion of the drinker refusing to acknowledge or at least minimizing the role of alcohol in his or her difficulties. Visual analogue scales provide a technique for measuring subjective experiences of this type. Subjects from a community-based voluntary agency and an alcohol treatment unit were asked to indicate the magnitude of their problems with alcohol on this scale. Both groups acknowledged high levels of problems with alcohol. Despite this, there was evidence of systematic bias in that half of the sample underestimated the severity of their drinking in comparison to an interviewer's rating using the same scale. A small group was identified that seemed to fit the stereotype of the alcoholic "denier" mentioned so frequently in the treatment literature. There was no relationship between "denial" and subsequent compliance with treatment.

Psychological symptoms, psychiatric disorder and alcohol dependence amongst men and women attending a community-based voluntary agency and an Alcohol Treatment Unit.

One-fifth of clients attending a community-based voluntary agency presented for treatment with an alcohol problem complicated by affective disorder, phobic anxiety or personality disorder. A matched sample of patients recruited from an Alcohol Treatment Unit, and assessed using the same stringent clinical criteria, had similar levels of formal psychiatric disorder, except for a small group of women. One quarter of women in this group were phobic with some overlap of affective disorder. Rates of psychological symptoms as opposed to psychiatric disorder were high in both samples and appeared to be associated with severity of dependence on alcohol. No sex differences were apparent in the rates of psychological symptoms. The practical as well as theoretical implications of these findings were discussed.

Glasgow Council on Alcohol: trends and developments in a community based voluntary organisation (1968-1989).

Since 1968, Glasgow Council on Alcohol has steadily increased the scope and variety of its efforts to help problem drinkers and their families. Apart from a large increase in client numbers over the last 20 years, there has been a number of interesting developments in identifying 'at risk' groups and directing them into the helping process. Prevention of alcohol problems has also become a major issue for this agency.

Characteristics and help-seeking patterns of attenders at a community-based voluntary agency and an alcohol and drug treatment unit.

The assumption that clients using community-based facilities in the form of Councils on Alcohol have less serious alcohol problems uncomplicated by the physical, social and psychological difficulties found in those attending Alcohol Treatment Units was not confirmed. One of the most striking findings were the similarities, rather than the differences between the two samples. Both groups had attenders who were heavily dependent on alcohol and were experiencing a wide range of problems. Attenders at both agencies, women as well as men, had help seeking patterns similar to those described for other populations which were discontinuous and uncoordinated and featured multiple contacts and simultaneous use of different services. The need for co-ordination was discussed in the light of the improved outcome which can be expected given appropriate matching of clients to treatment. Some suggestions as to how this might be achieved were discussed.