- Clinical and Laboratory Characteristics of Hyperprolactinemia in Children and Adolescents: National Survey. [Journal Article]
- JCJ Clin Res Pediatr Endocrinol 2018 Nov 05
- CONCLUSIONS: We present the largest cohort of children and adolescents with hyperprolactinemia in the literature thus far. Hyperprolactinemia is more common in females, and cabergoline is highly effective and practical to use in adolescents due to its biweekly dosing. Surgery indication should be revised in childhood.
- Repurposing of Bromocriptine for Cancer Therapy. [Journal Article]
- FPFront Pharmacol 2018; 9:1030
- Bromocriptine is an ergot alkaloid and dopamine D2 receptor agonist used to treat Parkinson's disease, acromegaly, hyperprolactinemia, and galactorrhea, and more recently diabetes mellitus. The drug ...
Bromocriptine is an ergot alkaloid and dopamine D2 receptor agonist used to treat Parkinson's disease, acromegaly, hyperprolactinemia, and galactorrhea, and more recently diabetes mellitus. The drug is also active against pituitary hormone-dependent tumors (prolactinomas and growth-hormone producing adenomas). We investigated, whether bromocriptine also inhibits hormone-independent and multidrug-resistant (MDR) tumors. We found that bromocriptine was cytotoxic towards drug-sensitive CCRF-CEM, multidrug-resistant CEM/ADR5000 leukemic cells as well as wild-type or multidrug-resistant ABCB5-transfected HEK293 cell lines, but not sensitive or BCRP-transfected multidrug-resistant MDA-MB-231 breast cancer cells. Bromocriptine strongly bound to NF-κB pathway proteins as shown by molecular docking and interacted more strongly with DNA-bound NF-κB than free NF-κB, indicating that bromocriptine may inhibit NF-κB binding to DNA. Furthermore, bromocriptine decreased NF-κB activity by a SEAP-driven NF-κB reporter cell assay. The expression of MDR-conferring ABC-transporters (ABCB1, ABCB5, ABCC1, and ABCG2) and other resistance-mediating factors (EGFR, mutated TP53, and IκB) did not correlate with cellular response to bromocriptine in a panel of 60 NCI cell lines. There was no correlation between cellular response to bromocriptine and anticancer drugs usually involved in MDR (e.g., anthracyclines, Vinca alkaloids, taxanes, epipodophyllotoxins, and others). COMPARE analysis of microarray-based mRNA expression in these cell lines revealed that genes from various functional groups such as ribosomal proteins, transcription, translation, DNA repair, DNA damage, protein folding, mitochondrial respiratory chain, and chemokines correlated with cellular response to bromocriptine. Our results indicate that bromocriptine inhibited drug-resistant tumor cells with different resistance mechanisms in a hormone-independent manner. As refractory and otherwise drug-resistant tumors represent a major challenge to successful cancer chemotherapy, bromocriptine may be considered for repurposing in cancer therapy.
- An Interesting Case of Hepatic Adrenocortical Carcinoma. [Journal Article]
- AMActa Med Indones 2018; 50(3):257-259
- Adrenocortical carcinoma (ACC) is a rare solid tumor with an incidence of 0.5 to 2 cases per million per year. It affects women more commonly than men with a ratio of 1.5:1. Ectopic ACC are considere...
Adrenocortical carcinoma (ACC) is a rare solid tumor with an incidence of 0.5 to 2 cases per million per year. It affects women more commonly than men with a ratio of 1.5:1. Ectopic ACC are considered to be extremely rare with no exact incidence data yet. We report an interesting case of hepatic ACC in a young woman with clinical signs of virilization.A-21-year old Sundanese woman visited our endocrine clinic with progressive hirsutism over the face, body, and extremities starting 14 years previously. She had irregular, heavy periods when she was 7 years old. She also experienced pubertal development of her breasts. However, both menstrual cycle and breast development ceased when she was 8 years old. She noticed voice deepening and alopecia. Physical examination showed male-type alopecia and intense hirsutism. Tanner stage was 3 for breast tissue and 5 for pubic hair. There was no galactorrhea. Body mass index was 21.4 kg/m2. Hormonal evaluation revealed increased level of free testosterone (>1500 ng/dl; NV: 8.4-48.1 ng/dl), dehydroepiandrosterone sulfate (>1000 ug/ml; NV: 65.1-369 ug/ml), and estradiol (533.60 pg/ml; NV: 14-124 pg/ml), low level of LH (<0.07 mIU/ml; NV: 1.7-11 mIU/ml) and FSH (<0.30 mIU/ml; NV: 1.34-9.40 mIU/ml), slight increased in morning serum cortisol (26.61 ug/ml; NV: 4.3-22.4 ug/ml), normal serum thyroid stimulating hormone (3.2 mIU/l; NV: 0.34-4.25 mIU/l) and prolactin (14.70 ng/ml; NV: 3.30-15.80 ng/ml). Gynecological ultrasound and brain MRI examination showed no structural abnormality. Abdominal CT scan demonstrated contrast enhanced solid inhomogenous mass sized 11.6 x 14.2 x 15.6 cm in right liver lobe. Neither suprarenal mass nor paraaortic lymphadenopathy was seen in the abdominal CT scan. Chromosomal examination revealed normal female karyotype (46, XX). Further liver biopsy showed morphology and immunohistochemistry (positive for CD 56, HEP 1, and NSE) consistent with adrenocortical carcinoma. Surgical therapy with referral to other institution was offered to the patient as first line treatment. Meanwhile, the patient got spironolactone 100 mg OD.Virilizing tumors are rare and few of them are androgen-producing adrenal tumors. Ectopic adrenal tumors are even rarer. Ectopic adrenal tissue can be found close to the adrenal glands, or along the path of descent or in association with gonad. Moreover, they have ever been reported in nervous system, stomach, gall bladder, and liver. There have been several case reports of adrenal rest tumor of liver; however, our literature review found no report of ectopic ACC of liver. Cortical tissue, embrologically derived from mesoderm, seems to be the sole component of the tumor which can undergo malignant transformation or become hormonally functional. Functioning tumors are more frequent in women. Our case demonstrated virilization as chief complaint. The ectopically located functioning tumors display the same clinical picture as tumors located in adrenal gland, with Cushing's syndrome and virilization are the most frequent symptoms in order of frequency. The virilization, as shown in our case, is due to excessive androgen production of dehydroepiandrosterone sulfate and testosterone. The distinction of ACC from benign adrenocortical tumor is important. Since there is no previous report of hepatic ACC and surgery is the keystone of curative treatment modality for ACC at adrenal gland, we planned the patient for surgical resection. Adjuvant treatment with chemotherapy (mitotane and combination of cytotoxic drugs), irradiation might be considered in ACC treatment. To control androgen effects, spironolactone was administered in our patient. However, there was no significant improvement in symptoms.In conclusion, we present the first reported case of hepatic ACC. A thorough history, physical examination, and appropriate laboratory, imaging examination are critical in evaluating virilized female patients. Elevated serum concentration of dehydroepiandrosterone sulfate and testosterone might direct clinician to functioning adrenal cortical tissue as etiology, with further investigation of exact tumor site.
- Etiological Profile of Galactorrhoea. [Journal Article]
- IJIndian J Endocrinol Metab 2018 Jul-Aug; 22(4):489-493
- CONCLUSIONS: Prokinetic use is the most common cause of galactorrhea in our study and often was investigated with costly tests and treated with D2 agonists unnecessarily. Hence, there is a need to ensure measures to reduce the non-specific use of prokinetics and increase awareness regarding the occurrence of galactorrhea with prokinetics use, to reduce unnecessary investigations and treatment.
- Amenorrhea as a Side Effect of Low Dose Aripiprazole: An Adolescent Case. [Case Reports]
- CPClin Psychopharmacol Neurosci 2018 Aug 31; 16(3):343-345
- Amenorrhea, oligomenorrhea, galactorrhoea, gynecomastia, infertility, and sexual dysfunction may arise as a consequence of hyperprolactinemia. Hyperprolactinemia is one of major side effects of treat...
Amenorrhea, oligomenorrhea, galactorrhoea, gynecomastia, infertility, and sexual dysfunction may arise as a consequence of hyperprolactinemia. Hyperprolactinemia is one of major side effects of treatment with antipsychotics, but aripiprazole is known as a dopamine stabilizer antipsychotic which can be used to improve hyperprolactinemia. In this report, it was described that an adolescent patient experienced amenorrhea after adding very low dose aripiprazole to ongoing fluoxetine treatment regime for major depressive disorder. Additionally, this case showed that the patient recovered from the amenorrhea with replacement of aripiprazole with quetiapine.
- A rare adverse drug reaction to escitalopram. [Journal Article]
- JFJ Family Med Prim Care 2018 Mar-Apr; 7(2):466-467
- Selective serotonin reuptake inhibitors are considered to be low side effect profile drugs as compared to conventional antidepressants. The primary care physicians should be aware of the rare and dep...
Selective serotonin reuptake inhibitors are considered to be low side effect profile drugs as compared to conventional antidepressants. The primary care physicians should be aware of the rare and depressing side effect of these drugs when they are prescribed in young, nonpregnant females. Mastalgia has been reported in <1% of the cases. Galactorrhea as an adverse drug reaction has been reported in very few case reports, and the frequency of this side effect is unknown.
- Hyperprolactinemia with Galactorrhea Due to Subclinical Hypothyroidism: A Case Report and Review of Literature. [Journal Article]
- CCureus 2018 May 31; 10(5):e2723
- Hyperprolactinemia is a common finding in primary hypothyroidism, but increased prolactin in the setting of subclinical hypothyroidism (SCH) has been scarcely reported in the literature. This is a ra...
Hyperprolactinemia is a common finding in primary hypothyroidism, but increased prolactin in the setting of subclinical hypothyroidism (SCH) has been scarcely reported in the literature. This is a rare case of hyperprolactinemia due to SCH that resolved with thyroid hormone replacement therapy. The patient was not on any medications known to cause hyperprolactinemia but she was using isoniazid for her latent tuberculosis. Isoniazid therapy may explain breast pain, but there is no reported relationship between isoniazid use causing subclinical hypothyroidism and hyperprolactinemia. A literature review reveals that few cases of galactorrhea associated with subclinical hypothyroidism have been reported. Similar to the reported cases in the literature, our patient's thyroid stimulating hormone (TSH) and prolactin levels returned to normal with levothyroxine therapy.
- Comparison of Male and Female Prolactinoma Patients Requiring Surgical Intervention. [Journal Article]
- JNJ Neurol Surg B Skull Base 2018; 79(4):394-400
- Objectives Prolactinomas are the most common functional pituitary adenoma. Symptoms of a prolactinoma stem from hormonal causes (menstrual irregularities, galactorrhea, and reduced libido) or from t...
Objectives Prolactinomas are the most common functional pituitary adenoma. Symptoms of a prolactinoma stem from hormonal causes (menstrual irregularities, galactorrhea, and reduced libido) or from tumor mass effect (visual changes and headache). Gender differences have been noted in prolactinomas, with males presenting with larger tumors and sequelae of mass effect, while females present commonly with hormonal symptoms. The purpose of this study is to evaluate differences in patient and disease characteristics, and outcomes between male and female prolactinoma patients undergoing surgery. Design This was a retrospective chart review. Setting This was done at the tertiary medical center. Participants The medical records of prolactinomas patients who underwent endoscopic endonasal surgery between March 2008 and August 2016 were reviewed. Main Outcome Measures Demographic information, tumor characteristics, and treatment characteristics and outcomes were collected. Statistical analysis was performed using chi-squared test or Student's t -test as applicable. Results Seventy-nine patients were identified, 22 males and 57 females. The average age for males was 38 years and for females was 35 years. Males were more likely to present with decreased libido ( p < 0.0001), whereas females more often presented with galactorrhea ( p < 0.0001) and menstrual irregularities. Tumor size was larger in males ( p = 0.0044) with higher likelihood of suprasellar extension ( p = 0.0409) and cavernous sinus invasion ( p = 0.0026). Males were more likely to have a subtotal resection rather than gross total resection ( p = 0.0086) and less likely to have normalization of prolactin levels following surgery ( p = 0.0019) Conclusion Male prolactinoma patients tend to have larger tumors with more aggressive features. This may have a role in the differences in outcomes noted in this study.
- Drugs and Lactation Database (LactMed) [BOOK]
- BOOKNational Library of Medicine (US): Bethesda (MD)
- Acupuncture at traditional Chinese medicine (TCM) sites used to treat low milk supply has been claimed to cause release of prolactin and oxytocin, although published studies have found mixed results ...
Acupuncture at traditional Chinese medicine (TCM) sites used to treat low milk supply has been claimed to cause release of prolactin and oxytocin, although published studies have found mixed results on serum prolactin. In one study, acupuncture did not affect prolactin hyperresponsiveness after stimulation with metoclopramide in women with amenorrhea-galactorrhea syndrome. Galactorrhea has been reported following acupuncture for pain treatment. No adverse effects on milk production were seen among lactating women who received acupuncture for postpartum sciatica. Acupuncture has been well described in TCM for treating insufficient milk supply, and is also recommended in some Western countries. Numerous studies found acupuncture at CV 17 (also referred to as Ren 17 or Shanzong; located at the center of the sternum), SI 1 (Shaoze; on the little finger), and ST 18 (Rugen; lower breast margins) to benefit women with a low postpartum milk supply. These studies generally do not meet current evidence-based guidelines, partly because of the extreme difficulty in double-blinding and placebo-controlling acupuncture studies. However, 2 studies did find a better response to electroacupuncture applied at a traditional site for lactation stimulation (SI 1) than electroacupuncture applied at a site unrelated to milk production (LI 1). None of the studies reported to date have made an attempt to optimize maternal nursing technique before acupuncture. Although less studied, acupressure at milk acupuncture sites has had similar effects. Galactogogues should never replace evaluation and counseling on modifiable factors that affect milk production. Acupuncture therapy has been used to treat breastfeeding for milk stasis (engorgement). Randomized, nonblinded studies in an outpatient Swedish lactation clinic compared routine care (including oxytocin spray) to routine care plus acupuncture at 2 or 3 points for treating milk stasis. A meta-analysis concluded that women who received acupuncture were less likely to develop an abscess, had less severe symptoms on day five, and had a lower rate of fever than women in the usual care group However, there is insufficient evidence from published trials to justify widespread implementation. A survey of 50 Swedish maternity units in 2007 found that 60% of hospitals used acupuncture to treat milk stasis, 18% used acupuncture to treat mastitis, and 2.2% each used it for painful breastfeeding or to improve milk supply. The authors felt that this extensive use was not justified based on the limited evidence for most of these uses. Auricular therapy uses stimulation of acupoints on the ear corresponding to various anatomical sites and functions of the body for the diagnosis, treatment, an prevention of disease. A systematic review of 26 studies on auricular therapy to increase milk supply included 3691 patients All studies applied vaccaria seed to press on ear acupoints. Overall, studies found a positive effect on milk production, onset of lactation, serum prolactin, breast fullness, neonate states, and frequency of newborn urination and defecation. No adverse effects were reported.
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- Drugs and Lactation Database (LactMed) [BOOK]
- BOOKNational Library of Medicine (US): Bethesda (MD)
- Little published information is available on the use of duloxetine during breastfeeding; however, the dose in milk is low and serum levels were low in two breastfed infants. An alternate drug that ha...
Little published information is available on the use of duloxetine during breastfeeding; however, the dose in milk is low and serum levels were low in two breastfed infants. An alternate drug that has been better studied may be preferred, especially while nursing a newborn or preterm infant. If duloxetine is required by the mother, it is not a reason to discontinue breastfeeding. Monitor the infant for drowsiness, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants and when using combinations of psychotropic drugs. Galactorrhea has been reported in women taking duloxetine.