Biomedical subjects

B M Biller

Publications and source records attributed to B M Biller.

35 records · Page 2Linked to original sources

PubMed1994

Pathogenesis of pituitary Cushing's syndrome. Pituitary versus hypothalamic.

There has been a long-standing controversy as to whether Cushing's syndrome is primarily a hypothalamic disorder, with the pituitary simply responding to excess of CRH or other factors, or whether the defect lies at the level of the pituitary. Current data suggest that in nearly all cases, the tumor is clonal, implying a genetic defect at the level of the pituitary. The specific abnormalities underlying the development of corticotroph adenomas remain to be determined. It is certainly possible that the historical controversy has created an artificial dichotomy in our thinking about the pathogenesis of Cushing's syndrome and that hypothalamic factors may play a permissive role in the clonal expansion of a mutated pituitary cell. Finally, the finding of polyclonality in hyperplastic corticotroph tissue from a patient with an ectopic CRH-secreting tumor suggests there may be a more direct role for CRH in the pathogenesis of Cushing's syndrome in rare cases.

Adenoma↗

PubMed1993

Significance of proliferating cell nuclear antigen index in predicting pituitary adenoma recurrence.

The recurrence rate of pituitary adenomas has been reported to be as high as 10% to 35% despite their generally benign nature. A monoclonal antibody directed against proliferating cell nuclear antigen (PCNA) was used to investigate whether the proliferative index might help to predict adenoma recurrence. This antigen is a nuclear protein identified as the auxiliary protein of deoxyribonucleic acid polymerase delta, and its gene expression correlates with cell proliferation. The authors studied 30 patients with recurrent pituitary adenomas, 32 with nonrecurrent adenomas, and seven normal pituitary tissue samples. The mean interval to recurrence ( +/- standard error of the mean) was 5.3 +/- 0.7 years. The age- and sex-matched nonrecurrent group had a mean follow-up period of 6.6 +/- 0.3 years without clinical recurrence. Mean percentages of PCNA-positive tumor nuclei in both the initial and the second surgical specimens of the recurrent adenomas (13.45% +/- 3.02% and 19.56% +/- 3.66%, respectively) were significantly higher than that of the nonrecurrent group (2.49% +/- 1.21%). In addition, recurrent tumors had a higher PCNA index than the initial tumors in the same patients. Normal anterior pituitary gland tissue had a significantly lower mean PCNA index (0.12% +/- 0.11%) than either patient group. Stepwise multivariate regression analysis indicated that factors which collectively correlated significantly with recurrence were: high PCNA index, large tumor size, extrasellar extension, and incomplete surgical excision. The PCNA nuclear count was not associated with age, sex, or hormone hypersecretion, but was higher in macro- than in microadenomas, in tumors with extrasellar extension, and in those incompletely excised. A higher PCNA index also correlated with a shorter disease-free interval. The authors conclude that evaluation of the PCNA index assists in predicting the likelihood of pituitary adenoma recurrence.

Adenoma↗

PubMed1992

Osteopenia in men with a history of delayed puberty.

BACKGROUND AND METHODS: The effect of delayed puberty on peak bone mineral density in men is unknown. To determine whether such a delay reduces normal peak bone density and leads to osteopenia during adulthood, we measured radial bone mineral density by single-photon absorptiometry and spinal bone mineral density by dual-energy x-ray absorptiometry in 23 men who had a history of constitutionally delayed puberty and 21 men who underwent normal puberty. Their mean ages were 26 and 24 years, respectively. The groups were matched for other factors known to affect bone mass. RESULTS: The mean (+/- SD) radial bone mineral density was significantly lower in the men with a history of delayed puberty than in the normal men (0.73 +/- 0.07 vs. 0.80 +/- 0.05 g per square centimeter; P less than 0.0002). Spinal bone mineral density was also significantly lower in the men with delayed puberty than in the normal men (1.03 +/- 0.10 vs. 1.13 +/- 0.11 g per square centimeter; P less than 0.003). Radial bone density was at least 1 SD below the mean value for the normal men in 15 of the 23 men with a history of delayed puberty, and spinal bone density was similarly decreased in 10 of the 23. CONCLUSIONS: Adult men with a history of constitutionally delayed puberty have decreased radial and spinal bone mineral density. These findings suggest that the timing of puberty is an important determinant of peak bone density in men. Because the peak bone mineral density achieved during young adulthood is a major determinant of bone density in later life, men in whom puberty was delayed may be at increased risk for osteoporotic fractures when they are older.

Absorptiometry, Photon↗

PubMed1992

Progressive trabecular osteopenia in women with hyperprolactinemic amenorrhea.

Reductions in cortical and trabecular bone mass have been documented in young women with hyperprolactinemic amenorrhea. It is unknown whether trabecular osteopenia is progressive or reversible with treatment of hyperprolactinemia. In addition, it is not known whether clinical or hormonal variables can predict trabecular bone density (BD) changes. Therefore, we investigated prospectively trabecular BD by computed tomography in 52 hyperprolactinemic women and 41 controls. The mean follow-up interval was 1.8 +/- 0.1 (SEM) yr. Patient groups were defined as follows: group 1, amenorrhea during the entire study; group 2, restoration of menses during the study by treatment of hyperprolactinemia; group 3, regular menses despite hyperprolactinemia, with no history of prior amenorrhea; group 4, history of prior amenorrhea, but menses restored with treatment of hyperprolactinemia before study entry; and group 5, oligomenorrhea. Groups 1, 2, and 4 had significant (P = 0.0006) initial spinal osteopenia [mean BD 141 +/- 7 (SEM), 144 +/- 9, and 151 +/- 5 mg/cc K2HPO4, respectively] compared with controls or with group 3 (170 +/- 4 and 173 +/- 8 mg/cc K2HPO4, respectively). Group 5 had an initial mean BD which was midway between that of the amenorrheic and eumenorrheic women (156 +/- 13 mg/cc K2HPO4). Group 1 had a significant (P = 0.04) decrease in mean BD to 132 +/- 8 mg/cc K2HPO4 over 1.7 +/- 0.2 yr, with BD in 42% of the group more than 2 SD below the control mean at the final study point. The mean BD in group 2 increased to 155 +/- 9 mg/cc K2HPO4, approaching significance (P = 0.07) when compared with the initial BD. Five of the nine patients in this group (56%) had an increase in BD greater than the variation expected for the computed tomography technique. However, 44% of the group 2 patients had a spinal BD which remained more than 1 SD below the normal mean. There was no change in BD in the other groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1992

Clonal origins of adrenocorticotropin-secreting pituitary tissue in Cushing's disease.

It is unclear whether Cushing's disease results from a primary pituitary disorder or arises in response to abnormal hypothalamic control of the pituitary gland. Clonal analysis can provide information as to whether neoplastic tissue is derived from a monoclonal proliferation of a genetically altered cell or from a polyclonal expansion of a group of cells affected by a common stimulus. We used X-linked restriction fragment length polymorphisms at the phosphoglycerate kinase, hypoxanthine phosphoribosyltransferase, and DXS255 loci in 11 women with biochemically and pathologically confirmed Cushing's disease to determine the clonal origins of corticotroph adenomas and corticotroph hyperplasia. Tumor tissue from all 10 women with morphologically and immunohistochemically confirmed ACTH-secreting pituitary microadenomas demonstrated a monoclonal pattern. Pathologically confirmed corticotroph hyperplasia in a patient with a CRH-secreting bronchial carcinoid was found to be polyclonal. We conclude that corticotroph microadenomas in Cushing's disease are monoclonal, supporting the theory that a spontaneous somatic mutation is the primary pathogenetic mechanism in this disorder. In addition, the demonstration of polyclonality in corticotroph hyperplasia implies that excess of hypothalamic hormones is an etiologic mechanism in cases of Cushing's syndrome associated with ectopic CRH-secreting tumors.

Adrenocorticotropic Hormone↗

PubMed1991

Osteopenia in women with hypothalamic amenorrhea: a prospective study.

Hypothalamic amenorrhea, a common disorder associated with abnormalities in gonadotropin pulsatility and subsequent estrogen deficiency, is usually transient, and treatment indications are unclear unless fertility is desired. To determine whether this disorder is associated with progressive bone loss, we studied 24 women with primary or secondary amenorrhea related to stress or simple weight loss, compared with 31 normal women of the same age. Amenorrheic women had significantly lower (P = .01) body fat (26.4 +/- 7.3 versus 30.6 +/- 4.7%) and higher (P = .0001) urine free cortisol levels (250 +/- 100 versus 140 +/- 50 nmol/day) than normals. Trabecular bone density in women with hypothalamic amenorrhea as assessed by spinal computed tomography was significantly (P = .001) lower than in normals (140.2 +/- 27.3 versus 175.1 +/- 24.6 mg K2HPO4/mL, respectively). Twenty of the 24 amenorrheic women had initial spinal bone density below the mean in normals, and in eight it was 2 standard deviations or more below the normal mean. Initial bone density correlated negatively with duration of amenorrhea (r = -0.489, P = .02) and positively with serum free testosterone levels (r = 0.517, P = .02). Prospective evaluation showed a decline in spinal bone density in those who were amenorrheic for fewer than 5 years. The slope of change in bone density correlated with initial weight, percent ideal body weight, and percent body fat (R2 = 0.597, P = .0003; R2 = 0.549, P = .0007; and R2 = 0.618, P = .0002, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Treatment of prolactin-secreting pituitary macroadenomas with the long-acting non-ergot dopamine agonist CV 205-502.

STUDY OBJECTIVE: Evaluation of the effects of an experimental long-acting non-ergot dopamine agonist, CV 205-502, on serum prolactin, tumor size, gonadal function, visual abnormalities, and tolerability in patients with macroprolactinomas. DESIGN: Prospective, unblinded, dose escalation as needed. SETTING: Four university medical centers; patients referred for treatment. PATIENTS: Twenty-six hyperprolactinemic patients (prolactin greater than 150 micrograms/L) with a pituitary macroadenoma were treated for 24 weeks with CV 205-502 given once daily. MEASUREMENTS AND MAIN RESULTS: Serum prolactin was measured at regular intervals. Prolactin levels decreased in all patients during treatment (mean pretreatment level, 2051.7 +/- 1077 micrograms/L [+/- SE]; 24 weeks, 39.0 +/- 11.3 micrograms/L; P = 0.0001); normal prolactin levels were achieved in 15 (58%). Tumor size decreased in 21 of 26 patients and ranged from 6% to 67% (mean, 19.2% +/- 3.4%). Onset or return of regular menses occurred in 11 of 15 premenopausal women, accompanied by an increase in estradiol concentrations (pretreatment, 186.5 +/- 25.0 pmol/L; on treatment, 690.9 +/- 104.3 pmol/L; P = 0.0003). Serum testosterone increased in 6 of 8 men; sexual function improved in 5 of 7 with pretreatment abnormalities. Two patients with reversible visual abnormalities improved within 2 weeks of starting treatment. Side effects occurred in 11 patients and abated over 1 to 2 weeks or after the dose was reduced. There was no evidence of toxicity as indicated by serial serum chemistries, liver function tests, hematologic profiles, thyroxine levels, and electrocardiogram studies. CONCLUSIONS: CV 205-502 reverses hyperprolactinemia and promotes reduction in tumor size with reversal of visual abnormalities and restoration of gonadal function in most patients. This compound will probably be useful in treating prolactinomas.

Adenoma↗

PubMed1990

Clinically nonfunctioning pituitary tumors are monoclonal in origin.

Clinically nonfunctioning pituitary adenomas are benign neoplasms comprising approximately 25-30% of pituitary tumors. Little is known about the pathogenesis of pituitary neoplasia. Clonal analysis allows one to make the important distinction between a polyclonal proliferation in response to a stimulatory factor versus a monoclonal expansion of a genetically aberrant cell. We investigated the clonal origin of pituitary tumors using X-linked restriction fragment length polymorphisms at the phosphoglycerate kinase and hypoxanthine phosphoribosyl-transferase genes. Restriction enzymes were used to distinguish maternal and paternal X-chromosomes, and combined with a methylation-sensitive restriction enzyme to analyze allelic X-inactivation patterns in six pituitary adenomas. All six tumors showed a monoclonal pattern of X-inactivation. These data indicate that nonfunctioning pituitary adenomas are unicellular in origin, a result consistent with the hypothesis that this tumor type is due to somatic mutation.

Adenoma↗

PubMed1990

Abnormal cortisol secretion and responses to corticotropin-releasing hormone in women with hypothalamic amenorrhea.

Hypothalamic amenorrhea (HA) is a common disorder associated with hypoestrogenemia and has adverse effects. The mechanism of GnRH deficiency in these women is not yet known. To investigate the role of the hypothalamic-pituitary-adrenal axis in HA, we studied 10 women [mean age, 29 +/- 7 (+/- SD) yr] with 0.5-13 yr of amenorrhea (mean, 4.3 +/- 3.7 yr) related to simple weight loss or psychological stress. We investigated cortisol and ACTH responses to a bolus of ovine CRH, 24-h plasma cortisol levels obtained every 10 min, and urinary free cortisol levels in these patients. Results were compared with those obtained in normal women during all phases of the menstrual cycle. We found that mean basal concentrations of cortisol were significantly higher (P = 0.03) in the HA patients (mean, 210 +/- 130 nmol/L) than in the normal women (100 +/- 30 nmol/L). The delta (peak - basal) cortisol was significantly lower (P = 0.004) in the HA patients than in the normal women (320 +/- 100 vs. 440 +/- 90 nmol/L, respectively). ACTH responses to CRH did not differ between HA patients and normal women. The 24-h mean cortisol was significantly higher (P = 0.006) in the HA patients than in the normal controls (280 +/- 50 and 220 +/- 50 nmol/L, respectively), due to higher cortisol levels at night. The urinary free cortisol level was significantly higher (P = 0.005) in the HA patients (230 +/- 70 nmol/day) than in normal women (150 +/- 40 nmol/day). We conclude that women with HA have a blunted cortisol response to CRH administration. In addition, they have hypercortisolism, as demonstrated by elevated 24-h mean serum cortisol levels and urinary free cortisol values. This hypothalamic-pituitary-adrenal axis activation in patients with stress or weight loss may be a mechanism in the development of amenorrhea and may relate to other potential adverse effects of HA.

Adrenocorticotropic Hormone↗

PubMed1989

Age and bone mass in premenopausal women.

It is important to determine the bone mass in normal premenopausal women because increasing numbers of conditions have been identified that result in premenopausal osteoporosis. The relationship between age and bone density was evaluated in 57 carefully characterized normal, premenopausal women using both single energy quantitative computed tomography (SEQCT) and dual energy (DEQCT). The mean bone density measurements were 172 mg/ml K2HPO4 SEQCT and 185 DEQCT. Bone density showed no statistically significant decline between age 18 and age 44. Single- and dual-energy data were highly correlated with each other (r = 0.89), and dual energy appeared to confer no advantage. There was an inverse relation between density and age of menarche. Bone density did not correlate with ideal body weight, percentage fat, or subcutaneous fat area.

Adolescent↗

PubMed1989

Body fat distribution measured with CT: correlations in healthy subjects, patients with anorexia nervosa, and patients with Cushing syndrome.

Computed tomography (CT) was used to study fat distribution in three groups of women of comparable age: 39 healthy volunteers, 15 patients with anorexia nervosa, and seven with Cushing syndrome. Patients with anorexia nervosa had a fivefold decrease in subcutaneous fat and only a twofold decrease in intraabdominal fat compared with the values for the volunteers. Patients with Cushing syndrome had less than a twofold increase in subcutaneous fat and greater than a fivefold increase in intraabdominal fat compared with values for the healthy subjects. These findings suggest that fat in different body compartments responds differently to disease processes and that CT can be used to measure these changes.

Adipose Tissue↗

PubMed1989

Gonadotropin and alpha-subunit responses to chronic gonadotropin-releasing hormone analog administration in patients with glycoprotein hormone-secreting pituitary tumors.

Pituitary tumors secreting intact glycoprotein hormones (LH, FSH, and TSH) and/or alpha-subunit are being increasingly recognized. Because chronic administration of GnRH analogs decreases gonadotropin secretion in normal subjects, we investigated gonadotropin and alpha-subunit responses to chronic GnRH analog administration in five men with glycoprotein hormone-secreting pituitary tumors. Two patients (patients A and B) received the GnRH agonist analog (D-Trp6-Pro9-NEt-LHRH) for 4 weeks as a daily sc dose (8 micrograms/kg.day). In both, secretion of LH and/or alpha-subunit increased markedly. Subsequently, three patients received a higher analog dose (32 micrograms/kg.day) for a longer duration (8 weeks). One patient with a LH- and FSH-secreting tumor (patient C) had a highly significant (P less than 0.001) fall in serum LH and FSH concentrations; however, alpha-subunit secretion increased. During a subsequent study, when this patient received a lower dose (8 micrograms/kg.day) for 8 weeks, gonadotropin suppression also occurred. In two additional patients who received this dose (32 micrograms/kg.day), it had a persistent agonist effect on FSH beta (patient D) and alpha-subunit secretion (patient E). A marked increase in alpha-subunit secretion occurred in all five patients, regardless of whether basal serum alpha-subunit concentrations were elevated. These patients received the GnRH analog at doses 2-8 times greater than those that suppress gonadotropin secretion in normal men. Serum LH and FSH concentrations decreased in only one patient with a gonadotropin-secreting adenoma. The serum LH and FSH responses to acute GnRH stimulation did not predict the gonadotropin responses to chronic GnRH analog administration. Thus, gonadotropin and alpha-subunit production by most pituitary adenomas is augmented during chronic GnRH analog administration, consistent with defective GnRH desensitization in the adenomatous tissue. Despite the heterogeneous gonadotropin responses to the GnRH analog in these patients, serum alpha-subunit levels increased in all patients, indicating dissociation in the secretion of intact gonadotropins and alpha-subunit.

Adenoma↗

PubMed1989

Mechanisms of osteoporosis in adult and adolescent women with anorexia nervosa.

Osteoporosis is a known consequence of anorexia nervosa (AN) in adults, but the mechanism of bone loss is not established, and there have been no studies of bone mass in women developing AN before attaining peak bone mass. To investigate the causes of bone loss in AN and to determine the consequences of developing AN during adolescence on bone mass, we compared the effects of AN on cortical and trabecular bone in 26 women with AN (19 adults, 18-42 yr old, and 7 adolescents, 14.9-17.0 yr old) using direct radial photon absorptiometry and both single and dual energy spinal computed tomography. The adult AN patients had marked spinal osteopenia [mean bone density, 120 +/- 28 (+/- SD) mg K2HPO4/cm3] compared with age-matched normal women (mean, 176 +/- 26 mg K2HPO4/cm3; P = 0.0001), which was severe (greater than 2 SD below the normal mean) in 50% of patients. Adult AN patients with the onset of amenorrhea before age 18 yr had significantly (P = 0.04) lower spinal bone density than those developing amenorrhea later (mean, 103 +/- 25 vs. 129 +/- 25 mg K2HPO4/cm3) independent of other variables correlated with bone density (duration of amenorrhea or urinary cortisol excretion). We found a negative correlation between spinal bone density and duration of amenorrhea (P = 0.006; r = -0.53). To determine the contribution of endogenous cortisol excess to the pathogenesis of the osteoporosis, urinary cortisol was measured. Urinary cortisol/creatinine clearance was significantly (P = 0.001) higher in AN patients than in normal women (mean, 2.7 +/- 1.2 vs. 1.0 +/- 0.3 nmol/L) and was negatively correlated (P = 0.03; r = -0.43) with bone mass. We conclude that AN affects trabecular bone and that both the onset of AN before attainment of peak bone mass and prolonged duration of amenorrhea result in more severe osteopenia. In addition to the significant contribution of hypogonadism, the cortisol excess that occurs in AN patients may contribute to the development of osteoporosis in these patients.

Adolescent↗

PubMed1988

Effects of prolactin and estrogen deficiency in amenorrheic bone loss.

To determine whether hyperprolactinemic women with menses are at risk for the development of osteopenia and to define the effects of PRL excess and estrogen deficiency on bone mass in amenorrheic women, spinal and radial bone densities were measured in 25 hyperprolactinemic women (13 with amenorrhea and 12 with regular menstrual periods) and 11 women with hypothalamic amenorrhea. The degree of hyperprolactinemia was comparable in the hyperprolactinemic women with and without menstrual periods [mean, 55 +/- 18 (+/- SD) and 57 +/- 16 micrograms/L, respectively]. The mean spinal bone density in the hyperprolactinemic amenorrheic women (148 +/- 26 mg/K2HPO4.cm3) was significantly lower (P less than 0.01) than that in 19 normal women (178 +/- 21 mg/K2HPO4.cm3), and 6 of the former group had values greater than 2 SD below normal. However, the mean spinal bone density in the eumenorrheic hyperprolactinemic women (171 +/- 22 mg/K2HPO4.cm3) was similar to that in the normal women and was significantly greater (P less than 0.05) than that in the hyperprolactinemic amenorrheic women. The mean spinal bone density in the women with hypothalamic amenorrhea (128 +/- 24 mg/K2HPO4.cm3) and normal PRL levels was also significantly (P less than 0.001) lower than that in normal women or hyperprolactinemic euenorrheic women. Six of the women with hypothalamic amenorrhea had bone density measurements greater than 2 SD below normal. The spinal bone density values were similar in the amenorrheic women with or without hyperprolactinemia. The mean radial bone density in the hyperprolactinemic women with amenorrhea (0.69 +/- 0.03 g/cm2) was comparable to that in the women with hypothalamic amenorrhea (0.69 +/- 0.05 g/cm2), and both groups had significantly (P less than 0.05) lower values than normal women (0.72 +/- 0.03 g/cm2). Radial bone density was normal in the hyperprolactinemic eumenorrheic women. The mean serum estradiol level in the hyperprolactinemic amenorrheic women (120 +/- 90 pmol/L) was significantly (P less than 0.05) lower than that in the hyperprolactinemic eumenorrheic women measured during the follicular phase of their cycles (240 +/- 180 pmol/L) and was comparable to that in the women with hypothalamic amenorrhea (80 +/- 40 pmol/L). Multiple comparisons of clinical variables, serum hormone concentrations, and bone mass demonstrated a significant correlation (P = 0.0125) between bone density and serum dehydroepiandrosterone sulfate levels, which suggests a role for endogenous androgens in the maintenance of premenopausal bone mass.(ABSTRACT TRUNCATED AT 400 WORDS)

Absorptiometry, Photon↗

PubMedDate not supplied

Medical therapy for prolactinomas and somatotroph adenomas.

OBJECTIVE: To review the current recommendations for medical treatment of prolactinomas and somatotroph adenomas. METHODS: The spectrum of symptoms of hyperprolactinemia and the clinical features of acromegaly are elaborated, and the various medical therapeutic options for management of prolactinomas and somatotroph adenomas are discussed. RESULTS: In patients with prolactinomas, medical therapy with a dopamine agonist constitutes the primary treatment and is usually associated with normalization of prolactin levels, tumor shrinkage, and resolution of clinical symptoms. For patients intolerant of bromocriptine, currently the only available dopamine agonist approved for prolactinomas in the United States, several other options can be explored. Somatotroph adenomas are treated first by using a transsphenoidal neurosurgical approach. For those patients not cured, medical therapy with octreotide, a somatostatin analogue, can be effective in biochemical and symptomatic control of the residual acromegaly. This medical option can be used in conjunction with radiation therapy while awaiting its effects or as the sole secondary therapy for this disorder. CONCLUSION: Medical therapy has an important role in the management of prolactinomas and somatotroph adenomas.

Journal Article↗

PubMedDate not supplied

Occult Leydig cell tumor in a patient with gynecomastia.

OBJECTIVE: To report a case of a clinically occult testicular tumor causing gynecomastia and to alert physicians to the importance of use of testicular ultrasonography in patients with progressive gynecomastia despite normal findings on testicular examination. METHODS: We present a detailed case, including results of clinical, laboratory, and radiologic assessment, of a man with hyperprolactinemia and gynecomastia. RESULTS: A 36-year-old man with progressive gynecomastia was referred to our clinic because of an increased serum prolactin level. Subsequent clinical investigation revealed no evidence of hypogonadism and several possible causes of the gynecomastia. Because of the patient's age and progressive symptoms, testicular ultrasonography was performed despite normal findings on testicular examination. This ultrasound study showed a right testicular mass, which proved to be a Leydig cell tumor. The patient was referred for definitive therapy with orchiectomy. Follow-up studies showed resolution of the gynecomastia and substantial decreases in prolactin and estradiol levels. CONCLUSION: Although gynecomastia is a relatively common disorder with a benign cause in most cases, physicians should be aware that normal findings on testicular examination do not completely rule out the possibility of a testicular tumor as the cause. Because of the potentially high morbidity of testicular tumors and their known association with gynecomastia, early performance of testicular ultrasonography in a patient with gynecomastia of unknown cause is advised.

Adult↗

PubMedDate not supplied

Hyperprolactinemia.

Prolactinomas are the most common pituitary tumors. Hyperprolactinemia is characterized by increased production of prolactin, often leading to reproductive dysfunction and galactorrhea. Prolactinomas may also cause male-factor infertility by producing hypogonadism. In addition, if large, they can produce neurologic symptoms by mass effect in the sellar area. The diagnostic evaluation first requires exclusion of other causes of hyperprolactinemia, such as pregnancy, primary hypothyroidism, numerous medications, and miscellaneous causes. The second step in the diagnostic evaluation is to perform a head scan, preferably an MRI. This is essential in order to exclude a "pseudoprolactinoma" which would require surgery. Following diagnostic evaluation, the next step is to determine whether a patient with hyperprolactinemia has an indication for therapy, such as a macroprolactinoma (tumor >1 cm), hypogonadism (risk of osteoporosis), infertility, significant galactorrhea, acne, hirsutism, or headache. The treatment of choice for nearly all patients with hyperprolactinemic disorders is medical. In most cases, dopamine agonists (bromocriptine, pergolide, cabergoline) are extremely effective in lowering serum prolactin, restoring gonadal function, decreasing tumor size, and improving visual fields. The main limitation is side effects, particularly nausea or orthostatic dizziness. The newest dopamine agonist, cabergoline, can be given just once or twice a week, is more effective in normalizing prolactin and restoring menses than bromocriptine, and is significantly better tolerated. However, it is not yet recommended as first-line therapy for patients seeking fertility, because adequate safety data in pregnancy are not available. For the infrequent patient unable to tolerate, or resistant to, medical therapy, neurosurgical transsphenoidal resection may be necessary, particularly if the patient has a large lesion jeopardizing the optic chiasm. Hyperprolactinemia is a rewarding disorder to manage because patients typically respond well to medication, with restoration of menses and fertility.

Bromocriptine↗