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Biomedical subjects

A B Grossman

Publications and source records attributed to A B Grossman.

At least 19 recordsLinked to original sources
PubMed2006

Growth hormone deficiency and replacement in patients with treated Cushing's Disease, prolactinomas and non-functioning pituitary adenomas: effects on body composition, glucose metabolism, lipid status and bone mineral density.

BACKGROUND/AIMS: This study was designed to determine whether previous Cushing's disease (CD) or prolactinoma (PRL) could exert adverse effects additional to those of growth hormone (GH) deficiency as a consequence of variable degrees of prior hypogonadism or hypercatabolism. We report the effects of 5 years GH treatment in 124 GH deficiency adults; 42 patients with non-functioning pituitary adenomas (NFPA), 43 with treated PRL and 39 with treated CD. METHODS: Fasting plasma glucose, HbA(1c), lipoprotein profile, anthropometry and bone mineral density (BMD) were measured at baseline, 6 months and annually up to 5 years. RESULTS: Mean body mass index remained unchanged in the PRL group and tended to increase in the NFPA group. In contrast, body mass index decreased in the CD group. Decreases in waist and waist/hip ratio were seen in all groups at 6 months. Decreases in total cholesterol and low-density lipoprotein cholesterol were seen in all groups and remained sustained at 5 years. Plasma glucose and HbA(1c) increased at 6 months. Subsequently, plasma glucose returned to baseline values at 5 years; in contrast, HbA(1c )remained unchanged at the end of the study. Baseline lumbar spine and hip BMD were lower in the PRL and CD groups than in the NFPA group, decreased over 1 year in all groups and subsequently increased by 2 years in NFPA with a subsequent increase in lumbar spine BMD in PRL and CD groups delayed to 3-5 years. CONCLUSIONS: Baseline characteristics and response to GH replacement are qualitatively similar in NFPA, PRL and CD patients. Because improvements in BMD occur later in PRL and CD patients, an extended trial of GH therapy may be indicated in those patients who were commenced on GH therapy as an additional treatment for reduced BMD.

Adenoma↗
PubMed2006

The discriminatory value of the low-dose dexamethasone suppression test in the investigation of paediatric Cushing's syndrome.

BACKGROUND: Low- and high-dose dexamethasone suppression tests (LDDST, HDDST) are used in the investigation of Cushing's syndrome (CS). In adults with Cushing's disease (CD), cortisol suppression during LDDST predicts suppression during the HDDST. METHODS: We reviewed the results of the LDDST (0.5 mg 6 hourly x 48 h), HDDST (2.0 mg 6 hourly x 48 h) and corticotrophin-releasing hormone (CRH) test in 32 paediatric patients with CS: 24 had CD, 1 ectopic ACTH syndrome, 5 nodular adrenal hyperplasia and 2 adrenocortical tumours. RESULTS: In CD, LDDST suppressed cortisol from 590.7 +/- 168.8 (mean +/- SD) to 333.7 +/- 104.0 nmol/l after 48 h (0 vs. 48 h, p < 0.05; mean suppression, 45.1%; CI (30.8, 59.4%); 16/24 (66%) suppressed >30%; mean suppression 68.1%, CI (58.1, 77.9%)). The HDDST suppressed cortisol from 596.3 +/- 174.5 to 47.1 +/- 94.8 nmol/l after 48 h (0 vs. 48 h, p < 0.05; mean suppression, 93.5%; CI (88.2, 98.8%) with 17/24 (71%) suppressing to <50 nmol/l and 100% to <50% of baseline). In the LDDST, suppression correlated with that during the HDDST (r = +0.45, p < 0.05) with >30% suppression predicting that in the HDDST and hence CD. CRH increased cortisol by +100.3% (CI 62, 138.5%), 22/24 (91.7%) showing a >20% increase. In the other CS pathologies (n = 8) the LDDST induced no significant decrease in cortisol. CONCLUSION: The LDDST was of diagnostic value by discriminating between CD and other CS aetiologies. In our view the HDDST is redundant in the investigation of paediatric CS.

Adolescent↗
PubMed2006

Linear growth and body mass index in pediatric patients with Cushing's disease or simple obesity.

BACKGROUND: Increasing prevalence of childhood obesity has resulted in an accelerating rate of referrals of overweight patients to pediatric clinics for exclusion of endocrine or metabolic etiologies. The exclusion of Cushing's disease (CD) requires complex and potentially invasive investigations. OBJECTIVE: To evaluate the sensitivity of accurate measurements of height, weight and body mass index (BMI) in discriminating between simple obesity and CD. METHODS AND PATIENTS: Height, weight and BMI were measured at diagnosis in 25 patients with CD; 14 males, 11 females, mean age 12.9 yr (6.4-17.8) and 41 patients with simple obesity (SO), defined as BMI >2.0 SD; 20 males, 21 females, mean age 9.4 yr (3.5-15.6). RESULTS: Mean (+/-SE) BMI SDS in the CD patients was 2.41+/-0.5 and in the SO patients 3.71+/-1.3. Height SDS in the CD patients was -1.88+/-0.24 and in the SO patients 1.18+/-0.19 (p<0.05). The mean (+/-SE) BMI SDS to height SDS ratio was significantly decreased in the CD compared with the SO patients; -1.81+/-0.54 vs +0.90+/-1.17 (p<0.0001). CONCLUSIONS: Simple, accurate measurement of height and BMI SDS values provides a quick, and sensitive diagnostic discriminator in pediatric patients with CD or SO, thus potentially avoiding complex investigations.

Adolescent↗
PubMed2006

Do corticosteroids damage the brain?

Corticosteroids are an essential component of the body's homeostatic system. In common with other such systems, this implies that corticosteroid levels in blood and, more importantly, in the tissues remain within an optimal range. It also implies that this range may vary according to circumstance. Lack of corticosteroids, such as untreated Addison's disease, can be fatal in humans. In this review, we are principally concerned with excess or disturbed patterns of circulating corticosteroids in the longer or shorter term, and the effects they have on the brain.

Adrenal Cortex Hormones↗
PubMed2005

Efficient short-term control of hypercortisolaemia by low-dose etomidate in severe paediatric Cushing's disease.

BACKGROUND: Paediatric Cushing's disease (CD) is rare, but is associated with considerable morbidity and requires effective treatment. Control of hypercortisolaemia is recommended prior to definitive therapy by transsphenoidal pituitary surgery with selective adenomectomy. We describe a 6.2-year-old male with severe hypercortisolaemia and life-threatening complications of Cushing's disease. Control of cortisol with metyrapone and ketoconazole was ineffective, and due to his deteriorating condition, the decision was taken to proceed to bilateral adrenalectomy. METHODS: Low-dose IV infusion of etomidate, with dose titration according to serum cortisol levels, was administered. RESULTS: Etomidate infusion (3.0 mg/h i.v.) decreased serum cortisol from 1,250 to 250 nmol/l within 24 h. Combined etomidate and hydrocortisone therapy was maintained to provide stable serum cortisol levels within the desired range for 12 days prior to successful bilateral adrenalectomy. CONCLUSION: In our experience, etomidate was effective and safe for short-term control of severe hypercortisolaemia in a severely ill child.

Adrenalectomy↗
PubMed2005

The aberrant expression of the gastric inhibitory polypeptide (GIP) receptor in adrenal hyperplasia: does chronic adrenocorticotropin exposure stimulate up-regulation of GIP receptors in Cushing's disease?

CONTEXT: Cortisol secretion is usually under the control of ACTH. However, cortisol secretion occurs in response to gastric inhibitory polypeptide (GIP) in rare cases of food-dependent Cushing's syndrome (CS). OBJECTIVE: We have investigated whether chronic ACTH stimulation or activation of the ACTH signaling pathway might be associated with GIP receptor (GIPR) expression. DESIGN: RT-PCR analysis and primary culture of hyperplastic adrenals. PATIENTS: All patients presented with CS: 20 unilateral adrenal adenomas, five Cushing's disease, one food-dependent CS. RESULTS: RT-PCR revealed GIPR expression in all hyperplastic adrenals studied. No RT-PCR product could be detected in two normal adrenals or 20 hyperfunctioning adrenal adenomas. Primary culture revealed a significant cAMP response to ACTH in all adrenals available for study (EC50, 8.1 x 10(-10) M in normals, 4.7 x 10(-10) M in Cushing's disease, and 4.4 x 10(-10) M in food-dependent disease). However, cultures taken from all four ACTH-dependent and the one food-dependent hyperplastic adrenals studied were also responsive to GIP (EC50 for cAMP, 1.3 x 10(-9) M in Cushing's disease and 4.1 x 10(-10) M in food-dependent disease). Fasting cortisol levels were low in the case of food-dependant Cushing's, rising postprandially as predicted. However, there was no trend toward low fasting or high postprandial cortisol in the other cases, suggesting that the presence of detectable GIPR alone, albeit with definite function in vitro, is not sufficient to cause clinically food-dependent CS. CONCLUSIONS: These data are consistent with the hypothesis that chronic ACTH stimulation or constitutive activation of the ACTH signaling pathway may be associated with aberrant GIPR expression, and suggest one mechanism for the pathogenesis of this phenomenon.

Adrenal Cortex↗
PubMed2005

Bone mineral density at diagnosis and following successful treatment of pediatric Cushing's disease.

Bone mineral density (BMD) is frequently reduced in children and adolescents with Cushing's disease (CD), but there is little follow-up data after cure. BMD was determined by dual energy X-ray absorptiometry (DEXA) in two groups of patients with CD. Group 1 comprised 8 patients, 5 males and 3 females, aged 12.4 yr (8.2-16.8), assessed at diagnosis. Group 2 comprised 11 subjects, 6 males and 5 females, diagnosed at age 13.3 yr (6.4-17.4), cured by transsphenoidal surgery (TSS) (no.=7) or TSS + pituitary irradiation (no.=4). They had measurement of BMD, at mean age of 18.3 yr (11.1-28.5), i.e. 4.5 yr (0.8-11.4) after cure. Four patients, mean age 20.2 yr (17.6-22.4), had repeated DEXA'scans, 1-4 times, for up to 5.8 yr. After cure, GH deficiency was present in 9 patients and treated with hGH in 8. In Group 1, patients' L2-L4 volumetric (v)BMD Z-score was variable with a mean of -1.04 (-3.21-0.11). L2-L4 vBMD Z-score values correlated negatively with midnight cortisol (p < 0.05). In Group 2, mean L2-L4 vBMD was -0.38 (-1.0-0.13); and in 7/11, mean femoral neck (FN) areal (a)BMD Z-score was 0.14 (-1.62-2.46). FN aBMD Z-score was higher than L2-L4 aBMD Z-score (p < 0.05). In patients with repeated scans, mean change in L2-L4 vBMD Z-score was 0.20 (-0.15-0.45), and mean change in FN aBMD Z-score 0.03 (-0.53-0.38). These findings show variability of BMD at diagnosis and near normal BMD after cure of pediatric CD, suggesting that with appropriate replacement of pituitary hormone deficiency normal peak bone mass is achievable.

Absorptiometry, Photon↗
PubMed2005

Final adult height and body mass index after cure of paediatric Cushing's disease.

OBJECTIVE: Linear growth data after cure of paediatric Cushing's disease (CD) have been reported infrequently. We evaluated final adult height (FH) and body mass index (BMI) in a cohort of paediatric patients treated successfully for CD. PATIENTS AND METHODS: Fourteen patients (10 male, age range 6.4-16.6 years) fulfilled the diagnostic criteria for CD. All had had transsphenoidal surgery (TSS), combined with pituitary irradiation (RT) (45 Gy in 25 fractions) in six. All were cured (post-TSS cortisol < 50 nmol/l or mean cortisol post-RT < 150 nmol/l). Subjects analysed had bone ages at diagnosis of < 15 'years' (male) and < 13 'years' (female). RESULTS: At diagnosis, height SDS was [mean (range)]-2.5 (-4.2 to -0.8) and body mass index (BMI) SDS +2.7 (0.8-5.1). Following cure, 13 patients had GH deficiency (peak GH < 20 mU/l) and were treated with hGH (+ GnRH analogue in four). Height SDS at FH (n = 10) or latest assessment (n = 4) was -1.3 (-3.9-0.2) and increased compared to diagnosis (P < 0.01). The difference between final or latest height SDS and target height SDS was -1.2 (-3.3-0.5), that is less (P < 0.01) than the difference between the height SDS at diagnosis and target height SDS of -2.4 (-3.9 to -0.5). At final height or latest assessment, BMI SDS was +1.7 (0.4-6.2), being decreased compared to diagnosis (P < 0.05) but greater than the normal population (P < 0.01). CONCLUSION: Catch-up growth was demonstrated in paediatric patients cured from CD, with the majority achieving FH within target height range. Early diagnosis and treatment of GH deficiency is recommended to achieve optimal long-term growth. Excess adiposity remains a potential long-term complication.

Adolescent↗
PubMed2005

Tumour surveillance imaging in patients with extrapituitary tumours receiving growth hormone replacement.

OBJECTIVE: GH replacement is widely used in the management of patients with adult-onset (AO)-GH deficiency (GHD). In most cases, AO-GHD arises as a result of pituitary/peripituitary tumours and/or their treatment, but the effect of GH replacement on recurrence/regrowth of these tumours is unknown. The aim of this study was to examine the effect of GH replacement in a group of patients with primary tumours of the parasellar region, many of which (e.g. craniopharyngioma, glioma or germ cell tumours) might be anticipated to have a higher recurrence rate than secretory and nonsecretory anterior pituitary tumours. PATIENTS AND DESIGN: We report here our experience of prospective imaging in 50 consecutive patients (21 males; mean age 45.9 years) with nonanterior pituitary parasellar tumours treated with GH. All had severe GHD (peak serum GH 9 mU/l or less on dynamic testing) and were treated with an identical dose-titration regimen to maintain serum IGF-I concentrations between the median and upper end of the age-adjusted normal range. The primary diagnoses were: craniopharyngioma (28), germ cell tumour (8), arachnoid cyst (4), meningioma (4), glioma (4) and mensenchymal tumour (2). External pituitary irradiation had been given to 37 (74%) of patients. Measurements Surveillance imaging (magnetic resonance imaging (MRI) 70%, computed tomography (CT) 16%, both 14%) was performed at baseline (prior to GH), at 6--12 months, and then again yearly or as clinically indicated. Median follow-up was 36 months (range 7--129 months). All images were reviewed by the same radiologist. RESULTS: Four patients had an apparent increase in tumour volume but in only one patient was it considered necessary to abandon GH replacement. In two of the four cases marginal increases in cystic parasellar tumours were not progressive; and in the fourth case apparent recurrence of a suprasellar germ cell tumour was shown to be acellular fibrous tissue only on biopsy. In all other cases either the appearances were unchanged or the amount of tissue was reduced during long-term follow-up on GH. CONCLUSIONS: Overall, GH appears safe with respect to tumour recurrence over this time period in this patient group. Comparison with similar prospective series in patients not receiving GH replacement is desirable.

Adult↗
PubMed2005

Enhanced protein kinase B/Akt signalling in pituitary tumours.

Pituitary tumours have previously been shown to harbour several abnormalities that cause deregulation of the cell cycle, particularly down-regulation of expression of the cyclin-dependent kinase inhibitor p27. However, it has been unclear whether these are the primary initiating events, or are secondary to other more proximate alterations in signalling pathways. In other cellular systems the Akt signalling pathway has been associated with downstream modulation of cell-cycle control. The aim of the present study was to test the hypothesis that Akt signalling is enhanced in pituitary tumours, and to see if changes in Akt expression are related to previous findings on low expression levels of the nuclear cell-cycle inhibitor p27 in pituitary tumours. We examined normal and adenomatous human pituitary tissue for mRNA and protein expression of Akt1, Akt2 and p27, and the activation of Akt, as well the phosphatase involved in the inactivation of Akt, phosphatase and tensin homologue deleted on chromosome 10 (PTEN). In pituitary adenomas Akt1 and Akt2 mRNA were found to be over-expressed compared with normal pituitary, while PTEN transcripts showed similar levels between the two tissue types. Immunohistochemical expression of phospho-Akt was found to be higher in the tumours than normal pituitaries, while the protein expression of nuclear p27 and PTEN was lower in the adenomas. However, the expression of p27 and Akt were not directly correlated. PTEN sequencing revealed no mutation in the coding region of the gene in pituitary adenomas, and thus we did not locate a cause for the increased phosphorylation of Akt. In summary, we have shown over-expression and activation of the Akt pathway in pituitary tumours, and we speculate that cell-cycle changes observed in such tumours are secondary to these more proximate alterations. Since Akt is a major downstream signalling molecule of growth factor-liganded tyrosine kinase receptors, our data are most compatible with an abnormality at this level as the primary driver of pituitary tumorigenesis.

Cell Cycle Proteins↗
PubMed2005

Treatment of advanced neuroendocrine tumours with radiolabelled somatostatin analogues.

Neuroendocrine tumours (NETs) constitute a heterogeneous group of tumours that frequently express cell membrane-specific peptide receptors, such as somatostatin receptors (SSTRs), and of which gastroenteropancreatic (GEP), carcinoid and pancreatic islet cell tumours exhibit the highest expression of SSTRs. Radiolabelled receptor-binding somatostatin analogues (octreotide and lanreotide) act as vehicles to guide radioactivity to tissues expressing SSTRs, and can thus be used for their diagnosis and treatment. After the localization of NETs bearing SSTRs with (111)In-octreotide (OctreoScan), a number of radioisotopes with different physical properties have been used for their treatment. The administration of high doses of the Auger electron and gamma-emitter (111)In-diethylenetriaminepenta-acetic acid (DTPA)(0),octreotide in patients with metastatic tumours has been associated with considerable symptomatic improvement but relatively few and short-lived objective tumour responses. The use of another radiolabelled somatostatin analogue coupled with (90)Y, a pure beta-emitter, (90)Y-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)(0),Tyr(3),octreotide ((90)Y-DOTATOC, OctreoTher), was associated with 10-30% objective tumour response rates, and appears to be particularly effective in larger tumours. (111)In- and (90)Y-DOTA-lanreotide has also been used for the treatment of NETs although its therapeutic efficacy is probably inferior to that of octreotide-based radiopharmaceuticals. More recently, treatment with (177)Lu-DOTA(0),Tyr(3)octreotate ((177)Lu-DOTATATE), which has a higher affinity for the SSTR subtype 2, resulted in approximately 30% complete or partial tumour responses; this radiopharmaceutical is particularly effective in smaller tumours. Furthermore, treatment using both (90)Y-DOTATOC and (177)Lu-DOTA(0),Tyr(3)octreotate seems promising, as the combination of these radiopharmaceuticals could be effective in tumours bearing both small and large lesions. Tumour regression is positively correlated with a high level of uptake on (111)In-octreotide scintigraphy, limited tumour mass and good performance status. In general, better responses have been obtained in GEP tumours than other NETs. The side effects of this form of therapy are relatively few and mild, particularly when kidney-protective agents are used. Treatment with radiolabelled somatostatin analogues presents a promising tool for the management of patients with inoperable or disseminated NETs, and particularly GEP tumours.

Humans↗
PubMed2005

Novel molecular aspects of pituitary adenomas.

Ghrelin stimulates while somatostatin inhibits GH release and they thus serve as functional antagonists. We have compared their effects on cell proliferation. Ghrelin stimulates while somatostatin inhibits cell proliferation in most tissues and cell lines. Here we show that ghrelin and desoctanoyl ghrelin stimulate cell proliferation in rat pituitary cell line (GH3), and these effects could be inhibited with mitogen-activated protein kinase (MAPK), tyrosine kinase and protein kinase C inhibitors. Somatostatin and its analogs negatively regulate the growth of pituitary cells, and we now show that they inhibit MAPK activation. We hypothesised that one of the mechanisms involved in the somatostatin effect is a stimulation of cell cycle inhibitor p27, as pituitary adenomas have decreased p27 peptide content. Both octreotide and a new somatostatin analog SOM230 treatment resulted in an upregulation of p27 protein levels in human somatotrophinoma cells. In summary, we suggest that ghrelin and somatostatin have opposite effects on somatotroph cells not just at the level of GH release but also in terms of cell proliferation. Ghrelin may play a role in pituitary tumorigenesis via an autocrine/paracrine pathway. Our results also suggest that the antiproliferative effect of somatostatin analogs octreotide and SOM230 involve the up-regulation of p27 and down-regulation of the MAPK pathway in human somatotrophinomas.

Adenoma↗
PubMed2004

Successful treatment of childhood-onset Cushing's disease is associated with persistent reduction in growth hormone secretion.

OBJECTIVE: Although Cushing's disease (CD) rarely occurs in childhood, affected children commonly fail to achieve predicted adult height. Hypercortisolaemia results in reduced GH secretion and GH-deficiency may persist or demonstrate delayed recovery after successful treatment of CD in adults. Whether recovery of spontaneous GH secretion occurs following treatment of childhood CD has yet to be established. DESIGN AND PATIENTS: We performed a retrospective analysis of the GH status of 13 children (10 males; 12.8 +/- 1.0 years, mean +/- SE) who had undergone successful treatment of CD that occurred prior to the completion of linear growth. Each underwent transsphenoidal hypophysectomy, resulting in satisfactory control of glucocorticoid levels in 7/13 (54%). The remaining six patients (46%) received fractionated external beam irradiation (4500 Gy). At the time of GH assessment, circadian dynamics of cortisol were normal in eight patients and five were receiving titrated glucocorticoid replacement. MEASUREMENTS: GH status was assessed using the peak response to a provocative stimulus. Eleven out of 13 underwent testing with insulin-induced hypoglycaemia (nadir plasma glucose </= 2.2 mmol/l) and glucagon provocation was used in 2/13. Severe GH-deficiency was defined as a peak GH response < 9 mU/l, and a normal response as > 30 mU/l. Intermediate values were taken to represent subnormal GH status. Assessment of GH status was performed 39 +/- 10 months (median +/- SE) following successful treatment (range 9-108 months). RESULTS: Using these criteria 4/13 (31%) patients had severe GH-deficiency. Only 2/13 (15%) had a normal response. 7/13 (54%) achieved peak GH levels in the subnormal range. Those with multiple pituitary hormone deficiencies were most likely to have lower peak GH levels, but there was no clear effect of pituitary irradiation or relationship between duration post cure and peak GH response. CONCLUSION: GH-deficiency is common and may persist for many years following successful treatment of CD prior to completion of linear growth. External radiotherapy does not necessarily result in severe GH-deficiency in the short term. Assessment of GH status and consideration of GH treatment should be considered following treatment of CD in childhood and adolescence in order to maximize the opportunities to achieve a satisfactory final adult height. In those with subnormal GH responses, continued assessment is necessary to determine whether the GH axis subsequently recovers or if these patients develop features of the adult GH-deficiency syndrome.

Adolescent↗
PubMed2004

PTSD symptoms and onset of neurologic disease in elderly trauma survivors.

In this case study, we present two Holocaust survivors who appeared to have adapted well post-trauma, but developed severe PTSD symptomatology following the onset of neurologic illness in later life. These individuals were referred fro neuropsychological evaluations by their treating neurologists to assess their levels of cognitive functioning. We present the neuropsychological findings, and discuss possible mechanisms for emergence of PTSD symptoms. These case studies demonstrate the need for systematic research to further investigate the potential relationship between aging, degenerative disease, and PTSD symptoms in elderly trauma survivors.

Age of Onset↗
PubMed2004

Clinical features, diagnosis, treatment and molecular studies in paediatric Cushing's syndrome due to primary nodular adrenocortical hyperplasia.

BACKGROUND: Primary nodular adrenocortical hyperplasia (PNAH) is a well recognized, but infrequently studied cause of paediatric Cushing's syndrome (CS). OBJECTIVE: To assess presentation, diagnosis, radiological imaging, treatment and molecular analysis of patients with childhood-onset CS due to PNAH. PATIENTS: Four males and two females (median age 12.9 years, range 10.9-16.9 years) were studied. RESULTS: All had growth failure (mean height SDS -1.2; range -2.5-0.0), weight gain [mean body mass index (BMI) SDS 3.5; range 2.5-4.6] and clinical virilization, while five had hypertension [mean systolic blood pressure (SBP) 130 mmHg, diastolic blood pressure (DBP) 83 mmHg]. One patient had generalized lentigines, one had a tibial chondromyxomatous cyst and two had facial freckling. One patient had a family history of primary nodular adrenocortical disease. The diagnosis of CS was based on elevation of sleeping midnight serum cortisol and urinary free cortisol excretion, and impaired suppression of cortisol on both low- and high-dose dexamethasone suppression tests (DST). All patients had undetectable plasma ACTH with absent responses of both plasma ACTH and serum cortisol to an intravenous (i.v.) corticotrophin-releasing hormone (CRH) test. Computed tomography or magnetic resonance imaging showed normal or small adrenals, with nodules in two patients. All patients underwent bilateral adrenalectomy, performed by open (n = 2) or laparoscopic surgery (n = 4) at a mean of 0.4 years (range 0.2-0.8 years) from diagnosis. Hypercortisolaemia was treated preoperatively by metyrapone alone 0.50-0.75 g/day (n = 4), metyrapone 0.75-1.50 g/day + o'p'DDD/mitotane 1-2 g/day (n = 1), or ketoconazole (n = 1). Adrenal histology showed nodular cortical hyperplasia with shrinkage of intervening cortical tissue and pigmentation, present in four patients. Molecular analysis of the type 1-alpha regulatory subunit of protein kinase A (PRKAR1A) gene revealed a novel germline mutation in one patient. Postadrenalectomy, three patients, had catch-up growth with height velocities increasing from 3.0, 3.9 and 2.5-8.9, 8.3 and 9.0 cm/years, respectively. All six are well at a follow-up (mean 4.0 years; range 0.5-10.8 years). CONCLUSIONS: PNAH was associated with cushingoid features, virilization and hypertension with a lack of cortisol suppression on high DST, undetectable plasma ACTH and absent cortisol and ACTH responses to CRH. Adrenals were normal or small on imaging. PRKAR1A gene analysis may be helpful in the assessment of these patients.

Adolescent↗
PubMed2004

Striant SR: a novel, effective and convenient testosterone therapy for male hypogonadism.

Striant SR (marketed as Striant in the US) is a novel sustained-release mucoadhesive buccal testosterone tablet for the treatment of male hypogonadism. Striant SR restores serum testosterone concentrations to the physiological range within 4 h of application, and steady-state concentrations are achieved within 24 h of twice-daily dosing. In phase III clinical trials, 87-97% of patients using Striant SR achieved 24-h-averaged serum testosterone concentrations within the normal range. In a comparative study, Striant SR was more likely to restore testosterone concentrations to the physiological range than Andropatch. In a small study, Striant SR produced steady-state testosterone concentrations comparable with those achieved with a testosterone gel (50mg testosterone). Striant SR was well tolerated, with a low incidence of adverse events and a low discontinuation rate (3.5%) due to adverse events in phase III studies. Striant SR is an effective, well-tolerated, convenient and discreet treatment for male hypogonadism.

Administration, Buccal↗
PubMed2004

Ghrelin: update on a novel hormonal system.

Ghrelin is a peptide hormone secreted into the circulation from the stomach but also synthesised in a number of tissues, suggesting both endocrine and paracrine effects. These include: stimulation of GH, prolactin and ACTH secretion; an increase in appetite; a diabetogenic effect on carbohydrate metabolism; positive inotropic effects on heart; vasodilatation; and effects on cell proliferation. The possibility of chronic manipulation of the ghrelin system on body weight, growth and appetite remains an exciting new field of exploration.

Amino Acid Sequence↗