Antipsychotic-Related Prolactin Levels and Sexual Dysfunction in Mentally Ill Youth: A 3-Month Cohort Study.

OBJECTIVE: Although these agents are used frequently, prospective data comparing serotonin/dopamine antagonists/partial agonists (SDAs) in youth regarding prolactin levels and sexual adverse effects (SeAEs) are scarce. METHOD: Youth aged 4 to 17 years, SDA-naive (≤1 week exposure) or SDA-free for ≥4 weeks were followed for ≤12 weeks on clinician's-choice aripiprazole, olanzapine, quetiapine, or risperidone. Serum prolactin levels, SDA plasma levels, and rating scale-based SeAEs were assessed monthly. RESULTS: Altogether, 396 youth (aged 14.0 ± 3.1 years, male participants = 55.1%, mood spectrum disorders = 56.3%, schizophrenia spectrum disorders = 24.0%, aggressive-behavior disorders = 19.7%; SDA-naive = 77.8%) were followed for 10.6 ± 3.5 weeks. Peak prolactin levels/any hyperprolactinemia/triple-upper-limit-of-normal-prolactin level were highest with risperidone (median = 56.1 ng/mL/incidence = 93.5%/44.5%), followed by olanzapine (median = 31.4 ng/mL/incidence = 42.7/76.4%/7.3%), quetiapine (median = 19.5 ng/mL/incidence = 39.7%/2.5%) and aripiprazole (median = 7.1 ng/mL/incidence = 5.8%/0.0%) (all p < .0001), with peak levels at 4 to 5 weeks for risperidone and olanzapine. Altogether, 26.8% had ≥1 newly incident SeAEs (risperidone = 29.4%, quetiapine = 29.0%, olanzapine = 25.5%, aripiprazole = 22.1%, p = .59). The most common SeAEs were menstrual disturbance = 28.0% (risperidone = 35.4%, olanzapine = 26.7%, quetiapine = 24.4% aripiprazole = 23.9%, p = .58), decreased erections = 14.8% (olanzapine = 18.5%, risperidone = 16.1%, quetiapine = 13.6%, aripiprazole = 10.8%, p = .91) and decreased libido = 8.6% (risperidone = 12.5%, olanzapine = 11.9%, quetiapine = 7.9%, aripiprazole = 2.4%, p = .082), with the least frequent being gynecomastia = 7.8% (quetiapine = 9.7%, risperidone = 9.2%, aripiprazole = 7.8%, olanzapine = 2.6%, p = 0.61), galactorrhea = 6.7% (risperidone = 18.8%, quetiapine = 2.4%, olanzapine = 0.0%, aripiprazole = 0.0%, p = .0008), and mastalgia = 5.8% (olanzapine = 7.3%, risperidone = 6.4%, aripiprazole = 5.7%, quetiapine = 3.9%, p = .84). Postpubertal status and female sex were significantly associated with prolactin levels and SeAEs. Serum prolactin levels were rarely associated with SeAEs (16.7% of all analyzed associations), except for the relationship between severe hyperprolactinemia and decreased libido (p = .013) and erectile dysfunction (p = .037) at week 4, and with galactorrhea at week 4 (p = .0040), week 12 (p = .013), and last visit (p < .001). CONCLUSION: Risperidone, followed by olanzapine, was associated with the largest prolactin elevations, with little prolactin-elevating effects of quetiapine and, especially, aripiprazole. Except for risperidone-related galactorrhea, SeAEs did not differ significantly across SDAs, and only galactorrhea, decreased libido, and erectile dysfunction were associated with prolactin levels. In youth, SeAEs are not sensitive markers for significantly elevated prolactin levels.

Gynecomastia.

Gynecomastia is common and may be asymptomatic. In most cases, a thorough history and physical examination, along with limited laboratory investigations, can help to exclude breast malignancy and serious underlying endocrine or systemic disease. Careful clinical observation may be all that is required in many cases, because gynecomastia often resolves spontaneously. Because gynecomastia is usually caused by an imbalance of androgenic and estrogenic effects on the breast, medical therapy may include antiestrogens, androgens, or aromatase inhibitors. Surgery is useful in the management of patients with long-standing symptomatic gynecomastia or when medical therapy is not successful.

Human adrenal cortex hyperfunction due to LH/hCG.

Adrenal cortex hyperfunction may occasionally be due to stimulation of steroid hormone production by LH/hCG. The recent demonstration of the LH/hCG receptor in a variety of normal and abnormal human adrenal tissues has provided a novel explanation for these clinical observations and offers the possibility of spontaneous remission (as in pregnancy-related hyperfunction) or effective treatment with GnRH-agonists (to down-regulate LH secretion in menopausal patients). Involvement of adrenal LH/hCG receptors should be considered in pregnant or post-menopausal patients with ACTH-independent Cushing's syndrome or androgen excess. Additional investigations are needed to better define the role of the LH/hCG receptor in the normal adult and fetal human adrenal and to understand how this system is excessively activated in rare cases of human disease.

New medications which decrease levothyroxine absorption.

OBJECTIVE: Medications may sometimes interfere with the intestinal absorption of levothyroxine, primarily by forming an insoluble complex with the thyroid hormone in the intestinal lumen. The goal of this study was to examine the acute effects of three previously unstudied medications on levothyroxine absorption. DESIGN: We studied the effects of three medications on thyroxine absorption in seven normal volunteers. On each study day, the subjects ingested 1 mg levothyroxine sodium, either taken separately or co-administered with sevelamer hydrochloride (Renagel, a phosphate-binding medication used in the treatment of hyperphosphatemia), chromium picolinate (an over-the-counter nutritional supplement), or ezetimibe (Zetia, a drug used in the treatment of hypercholesterolemia). Serum thyroxine was measured at intervals over a 6-hour period following drug ingestion. MAIN OUTCOME: Sevelamer hydrochloride and chromium picolinate each significantly (p < 0.05) decreased the area under the serum thyroxine concentration curve, while ezetimibe had no effect. CONCLUSION: Hypothyroid patients taking sevelamer hydrochloride or chromium picolinate should be advised to separate the time of ingestion of these drugs from their thyroid hormone preparation by several hours.

Endocrine and metabolic adverse effects of psychotropic medications in children and adolescents.

OBJECTIVE: Despite increasing use of psychotropic medications in children and adolescents, data regarding their efficacy and safety are limited. Endocrine and metabolic adverse effects are among the most concerning adverse effects of commonly used psychotropic medications. METHOD: Selective review of endocrine and metabolic effects of psychotropic medications in pediatric populations, with a focus on monitoring and management strategies. RESULTS: Because youth are still developing at the time of psychotropic drug exposure, most reference values need to be adjusted for gender and age. As in adults, youngsters receiving lithium require monitoring for thyroid dysfunction. Psychostimulants appear to cause mild reversible growth retardation in some patients, most likely because of decreased weight or slowing of expected weight gain; some patients may experience clinically significant reductions in adult height. Although still controversial, valproate use has been associated with an increased risk for polycystic ovary syndrome, in addition to causing weight gain. Although more data are required, children and adolescents appear to be at higher risk than adults for antipsychotic-induced hyperprolactinemia, weight gain, and possibly, associated metabolic abnormalities, which is of particular concern. CONCLUSIONS: Clinicians and caregivers need to be aware of potential endocrine and metabolic adverse effects of psychiatric medications. A careful selection of patients, choice of agents with potentially lesser risk for these adverse events, healthy lifestyle counseling, as well as close health monitoring are warranted to maximize effectiveness and safety.

Pheochromocytoma in a pregnant woman with a history of intracerebral aneurysms.

Pheochromocytoma in pregnancy is rare; if unrecognized, potentially fatal hypertensive crises may occur. We report a case of a 35-year-old woman with a history of two intracerebral aneurysms who presented at 26 weeks' gestation with tachycardia, hypertension, and pulmonary edema. Laboratory data revealed elevated 24-hour urinary catecholamine and metanephrine levels, and abdominal sonography showed a 10-cm right adrenal mass. After stabilization with phenoxybenzamine and metoprolol, cesarean section was successfully performed at 36 weeks' gestation. Postpartum abdominal computed tomography scanning confirmed a 10-cm right adrenal mass. A benign pheochromocytoma was removed without incident. This case illustrates the importance of early diagnosis and management of pheochromocytoma in pregnancy and is also an example of the rare association of pheochromocytoma with intracerebral aneurysms.

Effect of combination glipizide GITS/metformin on fibrinolytic and metabolic parameters in poorly controlled type 2 diabetic subjects.

OBJECTIVE: Epidemiological studies have implicated increased plasminogen-activated inhibitor 1 (PAI-1) as a marker or predictor of accelerated coronary atherosclerotic disease in type 2 diabetes. We sought to determine whether metabolic control, independent of its oral mode of implementation, affects PAI-1 in patients with marked hyperglycemia. RESEARCH DESIGN AND METHODS: A total of 91 subjects were screened, subjected to a 4-week drug washout, and randomized to daily treatment with glipizide GITS (maximum 20 mg, n = 46) or metformin (maximum 2,550 mg, n = 45) as monotherapy. After monotherapy, combination therapy was initiated by adding the second agent to the regimen. Plasma glucose (fasting and postprandial), HbA(1c), fructosamine, and PAI-1 were assayed before and after randomization and sequentially thereafter in all subjects; hepatic glucose output (HGO) and abdominal fat distribution were each measured in a subset of subjects. RESULTS: Glycemic control was markedly impaired at baseline (mean HbA(1c) 10.4 +/- 0.2% glipizide GITS; 10.0 +/- 0.2% metformin) but improved comparably with each agent as monotherapy and in combination (P < 0.0001 vs. baseline), as assessed with meal tolerance studies, fructosamine values, and HGO. Body weight and abdominal fat distribution did not change significantly in either group. PAI-1 concentrations were extraordinarily high (5- to 10-fold more than normal) at baseline (202 +/- 12 ng/ml glipizide GITS; 201 +/- 13 ng/ml metformin) but declined comparably, and significantly, after treatment with either agent as monotherapy and decreased further with combination therapy. CONCLUSIONS: When hyperglycemia is profound, increases in PAI-1 are also profound. Control of hyperglycemia with either glipizide GITS, an insulin secretagogue, or metformin as monotherapy comparably ameliorates elevated PAI-1.

Presence of luteinizing hormone/human chorionic gonadotropin receptors in male breast tissues.

Receptors for LH/human chorionic gonadotropin (hCG) have been found in a variety of nongonadal tissues including the female breast. Using in situ hybridization and immunohistochemistry, we demonstrated the presence of LH/hCG receptor mRNA and protein in normal male breast tissue obtained at autopsy (n = 4) and archival samples of benign gynecomastia (n = 14) and male breast carcinoma (n = 5). Although the function of these receptors remains to be determined, the findings suggest the possibility that LH and hCG may play a role in the pathogenesis of male breast disorders.

Gynecomastia: its features, and when and how to treat it.

Gynecomastia is common, being present in 30% to 50% of healthy men. A general medical history and careful physical examination with particular attention to features suggestive of breast cancer often suffice for evaluation in patients without symptoms or those with incidentally discovered breast enlargement. Men with recent-onset gynecomastia or mastodynia need a more detailed evaluation, including selected laboratory tests to search for an underlying cause. Treatment depends on the cause and may include observation, withdrawal of an offending drug, therapy of an underlying disease, giving androgen or antiestrogen drugs, or plastic surgery.

Gynaecomastia--pathophysiology, diagnosis and treatment.

Gynaecomastia (enlargement of the male breast tissue) is a common finding in the general population. Most cases of gynaecomastia are benign and of cosmetic, rather than clinical, importance. However, the condition might cause local pain and tenderness, could occasionally be the result of a serious underlying illness or a medication, or be inherited. Breast cancer in men is much less common than benign gynaecomastia, and the two conditions can usually be distinguished by a careful physical examination. Estrogens are known to stimulate the growth of breast tissue, whereas androgens inhibit it; most cases of gynaecomastia result from deficient androgen action or excessive estrogen action in the breast tissue. In some cases, such as pubertal gynaecomastia, the breast enlargement resolves spontaneously. In other situations, more active treatment might be required to correct an underlying condition (such as hyperthyroidism or a benign Leydig cell tumour of the testis) or medications that could cause breast enlargement (such as spironolactone) might need to be discontinued. For men with hypogonadism, administration of androgens might be helpful, as might antiestrogen therapy in men with endogenous overproduction of estrogens. Surgery to remove the enlarged breast tissue might be necessary when gynaecomastia does not resolve spontaneously or with medical therapy.

Osteoporosis and fracture risk in people with schizophrenia.

PURPOSE OF REVIEW: Excessive bone mineral density (BMD) loss has been associated with schizophrenia, but its mechanisms and clinical implications are less clear. The aim of this review was to summarize the risk of osteoporosis and bone fractures in schizophrenia patients. Moreover, we aimed to examine the impact of antipsychotic-induced hyperprolactinemia on bone metabolism. RECENT FINDINGS: Fifteen of 16 studies (93.8%) reported lower BMD or higher prevalence of osteoporosis in at least one region, or in at least one subgroup of schizophrenia patients compared with controls, but results were inconsistent across measured areas. Higher fracture risk was associated with schizophrenia in 2/2 studies (independently: n = 1), and 3/4 studies with antipsychotics. Reasons for this difference include insufficient exercise, poor nutrition, smoking, alcohol use, and low vitamin D levels. Altogether, 9/15 (60.0%) studies examining the relationship between antipsychotic-induced hyperprolactinemia and BMD loss found some effects of hyperprolactinemia. However, results were mixed, samples and effects were small, and only two studies were prospective. SUMMARY: Schizophrenia is associated with reduced BMD and fracture risk. Prevention, early detection, and intervention are required. The relative contributions of antipsychotic-related hyperprolactinemia and unhealthy lifestyle behaviors remain unclear, needing to be assessed in well designed, prospective studies, including bone turnover markers as intermediary endpoints.

Approach to the patient with gynecomastia.

Gynecomastia is a common and sometimes distressing condition that may occur in males of all ages. Although most cases have benign causes and many are self-limited, male breast enlargement may also be a sign of underlying systemic disease or drug toxicity. Although rare, male breast cancer must also be considered in the differential diagnosis. A careful diagnostic evaluation should be pursued, tailored to the individual patient's circumstances. Treatment may include reassurance, medication, or surgery.

Absorption of levothyroxine when coadministered with various calcium formulations.

BACKGROUND: Calcium carbonate is a commonly used dietary supplement and has been shown to interfere with levothyroxine absorption. However, calcium citrate, which is also used for supplementation purposes, has not been studied previously and calcium acetate, which is used to treat hyperphosphatemia in renal failure, has been reported to show little or no interference with levothyroxine absorption in a retrospective pharmacoepidemiologic study. We aimed to compare the effect of these three calcium formulations on levothyroxine absorption. MATERIALS AND METHODS: The study was conducted in eight healthy, euthyroid adults. We performed single-dose pharmacokinetic studies in which we measured levothyroxine absorption when given alone or when coadministered with calcium carbonate, calcium citrate, or calcium acetate in doses containing 500 mg elemental calcium. Serum thyroxine was measured at intervals over a 6-hour period after ingestion of the study drugs. RESULTS: Coadministration of each of the three calcium preparations significantly reduced levothyroxine absorption by about 20%-25% compared with levothyroxine given alone. CONCLUSIONS: Contrary to a prior report, our data suggest that calcium acetate interferes with levothyroxine absorption in a manner similar to that seen with calcium carbonate and calcium citrate. Although the effect of calcium is modest compared with some other medications previously studied, hypothyroid patients should be cautioned to take their levothyroxine well-separated from all of these calcium formulations.

Rupture of a craniopharyngioma cyst following trauma: a case report.

There have been only 20 reported cases of non-surgical rupture of a craniopharyngioma cyst, with only 3 cases secondary to trauma. Here we present a rare case of temporary shrinkage of a cystic craniopharyngioma following head trauma. After a motor vehicle accident in May 2001, a 61-year old woman began to have blurred vision and headaches. Magnetic resonance imaging (MRI) of the head revealed a primarily cystic mass measuring approximately two centimeters, involving the sellar and suprasellar area with compression of the pituitary. Visual field testing showed a left hemianopsia and the patient was referred for surgical evaluation. Transsphenoidal drainage of the cystic lesion in November 2001 provided histologic confirmation of the craniopharyngioma. Post-operative MRI showed cyst reduction and visual fields improved. Late in 2002, the patient again experienced progressive visual loss. Repeat MRI revealed a recurrent cystic craniopharyngioma, now measuring approximately three centimeters with subfrontal and parasellar extension and compression of the optic chiasm. A bifrontal surgical approach was advocated; however, prior to the scheduled surgery, the patient sustained a fall with trauma to the head. Following this event she experienced dramatic improvement in her headache and vision and repeat MRI showed the cystic lesion to be significantly decreased in size. Spontaneous rupture of craniopharyngioma cysts is uncommon but has been reported with increasing frequency. It is, however, exceedingly rare for a cyst to rupture following trauma.

IgE antithyroid antibodies in patients with Hashimoto's disease and chronic urticaria.

Although chronic urticaria may be associated with the presence of serum anti-thyroid antibodies, it is not known whether these antibodies play a causal role in the urticaria. We therefore sought to determine whether the anti-thyroid antibodies seen in patients with urticaria were of the IgE class. Using commercial ELISA kits for measuring serum IgG anti-thyroglobulin and anti-thyroid peroxidase antibodies, we modified the procedure to detect IgE antibodies. We examined sera from 20 patients with urticaria who had IgG anti-thyroid antibodies and from 12 patients with IgG antithyroid antibodies who did not have urticaria. Only 2 of 20 patients with urticaria and IgG anti-thyroid antibodies had detectable IgE anti-thyroid antibodies: 1 patient had anti-thyroid peroxidase IgE antibody and 1 patient had anti-thyroglobulin IgE. IgE anti-thyroid antibodies do not appear to play a causal role in urticaria in the majority of patients.