Endocrinology and Metabolism

Original Articles

Reduction of Central Dopamine Release in Hyperprolactinemia.: Bong Soo Cha, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh, Su Youn Nam, Eun Jig Lee, Bong Chul Chung, Jung Han Kim, Sei Chang Oh; J Korean Endocr Soc. 1996;11(3):277-284. Published online November 7, 2019

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Abstract PDF: Background
Prolactin(PRL) secretion is tonically inhibited by doparnine that originates from the hypothalamic tuberoinfundibular tract and reaches the lactotroph via the hypophyseal portal vessel. Hyperprolactinemia associated with oligomenorrhea-amenorrhea, galactorrhea and/or infertility is mainly due to PRL-secreting pituitary adenoma(PA). The diagnosis of idiopathic hyperprolac- tinemia(IHP) is made, when hyperprolactinemia is sustained and all causes of hyperprolactinemia are excluded without radiological abnormality. It is not known, whether IHP and PA are two distinct entities or two subsequent phases of the same disease. The etiology of both disorders remains unresolved. We investigated that PRL hypersecretion in patients with IHP and PA may be the result of a defect in the central nervous system(CNS)-dopamine release, and that there may be some differences in pathogenesis of both diseases. Methods: We measured 24 hour-urinary dopamine, norepinephrine, epinephrine, and serum and 24 hour-urinary VMA(vanillyl rnandelic acid), HVA(homovanilic acid), DOPAC(3,4-dihydroxy phenylaceticacid), MHPG(3-methoxy 4-hydroxy phenylglycol) in 10 normal controls, 9 patients with IHP, and 17 patients with PA in the early follicular phase. Results: Urinary HVA and DOPAC concentrations, the major metabolites of CNS dopaminergic activity, were signficantly lower in both patients with IHP and PA compared with those in normal controls(p 0.05), whereas they were not different in both disease groups. Dopamine, norepine-phrine, epinephrine, MHPG concentrations were similar to those of the normal controls. Although VMA concentrations of both disease groups were significantly higher than those of normal controls, all of them were within normal range. Conelusion: Although our data are unable to establish the precise biochemical defect responsible for central dopamine deficiency in pathogensis of IHP and PA, we can support the presence of a pathological reduction of brain dopamine activity in IHP and PA.

Adrenal gland
Early Prediction of Long-Term Response to Cabergoline in Patients with Macroprolactinomas: Youngki Lee, Cheol Ryong Ku, Eui-Hyun Kim, Jae Won Hong, Eun Jig Lee, Sun Ho Kim; Endocrinol Metab. 2014;29(3):280-292. Published online September 25, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.3.280

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Abstract PDF PubReader

Background

Cabergoline is typically effective for treating prolactinomas; however, some patients display cabergoline resistance, and the early characteristics of these patients remain unclear. We analyzed early indicators predicting long-term response to cabergoline.

Methods

We retrospectively reviewed the cases of 44 patients with macroprolactinomas who received cabergoline as first-line treatment; the patients were followed for a median of 16 months. The influence of various clinical parameters on outcomes was evaluated.

Results

Forty patients (90.9%) were treated medically and displayed tumor volume reduction (TVR) of 74.7%, a prolactin normalization (NP) rate of 81.8%, and a complete response (CR; TVR >50% with NP, without surgery) rate of 70.5%. Most patients (93.1%) with TVR ≥25% and NP at 3 months eventually achieved CR, whereas only 50% of patients with TVR ≥25% without NP and no patients with TVR <25% achieved CR. TVR at 3 months was strongly correlated with final TVR (R=0.785). Patients with large macroadenomas exhibited a low NP rate at 3 months, but eventually achieved TVR and NP rates similar to those of patients with smaller tumors. Surgery independently reduced the final dose of cabergoline (β=-1.181 mg/week), and two of four patients who underwent surgery were able to discontinue cabergoline.

Conclusion

Determining cabergoline response using TVR and NP 3 months after treatment is useful for predicting later outcomes. However, further cabergoline administration should be considered for patients with TVR >25% at 3 months without NP, particularly those with huge prolactinomas, because a delayed response may be achieved. As surgery can reduce the cabergoline dose necessary for successful disease control, it should be considered for cabergoline-resistant patients.

Citations

Citations to this article as recorded by

Resistance to dopamine agonists in the treatment of prolactinomas: diagnostic criteria, mechanisms and ways to overcome it
Irena A. Ilovayskaya, Gulnar R. Vagapova
Almanac of Clinical Medicine.2024; 51(7): 397. CrossRef
Diagnosis and management of prolactin-secreting pituitary adenomas: a Pituitary Society international Consensus Statement
Stephan Petersenn, Maria Fleseriu, Felipe F. Casanueva, Andrea Giustina, Nienke Biermasz, Beverly M. K. Biller, Marcello Bronstein, Philippe Chanson, Hidenori Fukuoka, Monica Gadelha, Yona Greenman, Mark Gurnell, Ken K. Y. Ho, Jürgen Honegger, Adriana G.
Nature Reviews Endocrinology.2023; 19(12): 722. CrossRef
Outcome Measures for Medical and Surgical Treatment of Prolactinomas. Is the Role of Surgery Underestimated?
Andrius Anuzis, Kevin O. Lillehei
Journal of Neurological Surgery Part B: Skull Base.2023;[Epub] CrossRef
Are dopamine agonists still the first-choice treatment for prolactinoma in the era of endoscopy? A systematic review and meta-analysis
Xiangming Cai, Junhao Zhu, Jin Yang, Chao Tang, Zixiang Cong, Chiyuan Ma
Chinese Neurosurgical Journal.2022;[Epub] CrossRef
Italian Association of Clinical Endocrinologists (AME) and International Chapter of Clinical Endocrinology (ICCE). Position statement for clinical practice: prolactin-secreting tumors
Renato Cozzi, Maria Rosaria Ambrosio, Roberto Attanasio, Claudia Battista, Alessandro Bozzao, Marco Caputo, Enrica Ciccarelli, Laura De Marinis, Ernesto De Menis, Marco Faustini Fustini, Franco Grimaldi, Andrea Lania, Giovanni Lasio, Francesco Logoluso, M
European Journal of Endocrinology.2022; 186(3): P1. CrossRef
Biochemical Remission after Cabergoline Withdrawal in Hyperprolactinemic Patients with Visible Remnant Pituitary Adenoma
Kyungwon Kim, Yae Won Park, Daham Kim, Sung Soo Ahn, Ju Hyung Moon, Eui Hyun Kim, Eun Jig Lee, Cheol Ryong Ku
The Journal of Clinical Endocrinology & Metabolism.2021; 106(2): e615. CrossRef
Surgery is a safe, effective first-line treatment modality for noninvasive prolactinomas
Ji Yong Park, Wonsuk Choi, A Ram Hong, Jee Hee Yoon, Hee Kyung Kim, Woo-Youl Jang, Shin Jung, Ho-Cheol Kang
Pituitary.2021; 24(6): 955. CrossRef
Molecular Pathways in Prolactinomas: Translational and Therapeutic Implications
Betina Biagetti, Rafael Simò
International Journal of Molecular Sciences.2021; 22(20): 11247. CrossRef
A scoping review to understand the indications, effectiveness, and limitations of cabergoline in radiological and biochemical remission of prolactinomas
Rakesh Mishra, SubhasK Konar, Adesh Shrivastava, Pradeep Chouksey, Sumit Raj, Amit Agrawal
Indian Journal of Endocrinology and Metabolism.2021; 25(6): 493. CrossRef
Predictors of dopamine agonist resistance in prolactinoma patients
Elle Vermeulen, Jean D’Haens, Tadeusz Stadnik, David Unuane, Kurt Barbe, Vera Van Velthoven, Sven Gläsker
BMC Endocrine Disorders.2020;[Epub] CrossRef
The Role of Dopamine Agonists in Pituitary Adenomas
Erica A. Giraldi, Adriana G. Ioachimescu
Endocrinology and Metabolism Clinics of North America.2020; 49(3): 453. CrossRef
Prevalence of Thyroid Disease in Patients Surgically Treated for Pituitary Disease
Kim, Cho, Ku, Jung, Moon, Kim, Shin, Kim, Lee
Journal of Clinical Medicine.2019; 8(8): 1142. CrossRef
Articles in 'Endocrinology and Metabolism' in 2014
Won-Young Lee
Endocrinology and Metabolism.2015; 30(1): 47. CrossRef

Case Report

Hyperprolactinemia-Associated Breast Uptake of Radioiodine Following 131I Postablation Scan in Differentiated Thyroid Cancer.: Jae Hee Ahn, Sun Young Kim, Ye Ji Kim, Suk Young Lee, Jae Hyoung Lee, Seung Hun Kang, Ho Cheol Hong, Sae Jeong Yang, Hye Jin Yoo, Ji A Seo, Sin Gon Kim, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi, Hae Yoon Choi; Endocrinol Metab. 2011;26(4):345-347. Published online December 1, 2011; DOI: https://doi.org/10.3803/EnM.2011.26.4.345

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Abstract PDF

Scanning with whole-body 131I scintigraphy after surgery has been a valuable diagnostic modality in the surveillance of patients with differentiated thyroid cancer. Radioiodine uptake is rarely observed in non-lactating breast tissue, which mimics thyroid cancer metastasis. We now report a case of a 45-year-old female thyroid cancer patient who underwent radioiodine therapy, and in whom breast uptake of radioiodine was observed on a post-therapy whole body scan. Her serum prolactin level was elevated to 328 ng/mL at the time of the radioiodine uptake, and the hyperprolactinemia was induced by her antipsychotic medications. Six months after she discontinued that medication, her serum prolactin level was normalized to 12.6 ng/mL and breast uptake of iodine was no longer present in a follow-up whole body scan.

Citations

Citations to this article as recorded by

Incidental Findings of Intense Radioiodine Uptake in Struma Ovarii and Bilateral Nonlactating Breasts Simultaneously on Postablation 131I SPECT/CT for Papillary Thyroid Cancer
Hye-kyung Shim, Mi Ra Kim
Nuclear Medicine and Molecular Imaging.2016; 50(4): 353. CrossRef

Original Articles

The Clinical Characteristics of Macroprolactinemia.: Young Ju Choi, Jun Goo Kang, Sung Yeon Kim, Eui Sil Hong, Sang Wan Kim, Chan Soo Shin, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee; J Korean Endocr Soc. 2005;20(3):216-223. Published online June 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.3.216

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Abstract PDF: BACKGROUND
Prolactin has been identified by gel chromatography to exist is three different forms in human serum; monomeric prolactin(molecular mass 23kDa), big prolactin (molecular mass 50~60 kDa) and big big prolactin, otherwise known as macroprolactin(molecular mass 150~170kDa). The predominance of macroprolactinemia has long been known in idiopathic hyperprolactinemic patients with maintained fertility. In recent reports, 24% of microprolactinoma patients showed no menstrual disturbances, which was suggestive of macroprolactinemia. The purpose of this study was to evaluate: (1) the frequency of macroprolactinemia among idiopathic hyperprolactinemia and prolactinoma patients, (2) the difference in the clinical characteristics between hyperprolactinemia, with and without macroprolactinemia, among idiopathic hyperprolactinemia and prolactinoma patients, and (3) the follow-up prolactin level using the bromocriptine response. METHODS: We retrospectively analyzed the clinical characteristics and prolactin levels in 43 idiopathic hyperprolactinemia and 51 prolactinoma patients with a poor bromocriptine response. Macroprolactinemia was identified by the prolactin recovery of < 40% using the polyethylene glycol(PEG) precipitation test. RESULTS: (1) Of the 43 idiopathic hyperprolactinemia and 51 prolactinoma patients, 17(39.5%) and 9(17.6%), respectively, were macroprolactinemic(P<0.05). (2) Among the idiopathic hyperprolactinemia patients, galactorrhea combined with amenorrhea was significantly less frequent (P<0.05), with the 1- and 2-year follow-up prolactin levels being significantly higher in those with macroprolactinemia than monomeric prolactinemia(P<0.05). (3) Among the prolactinoma patients, amenorrhea was significantly less frequent(P<0.05), but asymptomatic cases were more frequent in those with macroprolactinemia than monomeric prolactinemia(P <0.05). The 1- and 2-year follow-up prolactin levels were significantly higher in those with macroprolactinemia than monomeric prolactinemia(P<0.05). CONCLUSION: The screening of macroprolactinemia should be considered in idiopathic hyperprolactinemia and prolactinoma patients with a poor bromocriptine response

Comparison of Treatment Modalities in Hyperprolactinemia.: Sun Hee Park, Hyeon Jeong Jeon, Do Joon Park, Kyong Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee; J Korean Endocr Soc. 2002;17(1):32-42. Published online February 1, 2002

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Abstract PDF: BACKGROUND
Prolactinomas have been treated primarily with bromocriptine, a dopamine agonists, rather than by transsphenoidal pituitary adenomectomy. However, lower success rates, as well as intolerance or resistance to medical therapy, have been reported in some recent series. The purpose of this study was to compare the effects of surgery and bromocriptine in the treatment of prolactinomas patients. Also we investigated the natural history and effects of bromocriptine on patients with idiopathic hyperprolactinemia. METHEODS: We retrospectively compared the effects of treatment with surgery and with bromocriptine in 27 idiopathic hyperprolactinemia patients, 35 microprolactinoma patients and 61 macroprolactinoma patients. RESULTS: (1) In 14 patients with untreated idiopathic hyperprolactinemia, 8 (57%) achieved remission. In patients without remission, preoperative serum prolactin level was significantly higher than patients with remission (p<0.05). In 13 patients on bromocriptine, 11 (85%) achieved remission, while the other 2, taking bromocriptine irregularly because of side effects, had persistent hyperprolactinemia. (2) In 35 patients with microprolactinoma, 11 (30%) surgery as initial therapy and surgical remission was achieved in only 5 of the 11 (45%). In 23 patients on bromocriptine, 17 (74%) achieved remission. Among the 6 patients without remission, 5 patients took bromocriptine irregularly because of side effect. (3) In 61 patients with macroprolactinoma, 49 (80%) underwent surgery as initial therapy and surgical remission was achieved in only 9 of the 49 (18%). In 50 patients on bromocriptine, 30 (60%) achieved remission. Among the 20 patients without remission, 13 took bromocriptine irregularly because of side effect and 5 were resistant to bromocriptine. CONCLUSION: In idiopathic hyperprolactinemia, the requirement for medical treatment is doubtful because of a high tendency to ward spontaneous cure. In spite of the low success rate, surgery has been used as the primary therapy for prolactinoma in Korea. And yet, medical treatment with bromocriptine is superior to surgery. However, irrgular administration of medication due to drug side effects was the main cause of the low success rate. Therefore, the necessity for new drug development is emphasized

Case Reports

A Case of McCunt-Albright Syndrome Associated with Acremegaly and Fibrous Dysplasia.: Jung Guk Kim, Sung Woo Ha, Sang Won Chung, Seong Mo Koo, Jae Tae Lee, Kyu Bo Lee, Yong Sun Kim, Sam Kwon, Bo Wan Kim; J Korean Endocr Soc. 1998;13(1):108-114. Published online January 1, 2001

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Abstract PDF: Acromegaly and hyperprolactinemia have been described in association with polyostotic fibrous dysplasia. The pathogenic mechanisms of this endocrinopathy are not clear. We experienced a 19-year-old male with hypersecretion of GH, hyperprolactinemia and fibrous dysplasia. He was referred for evaluation of suspected acromegaly. He had no skin pigmentation. Plasma GH, PRL, somatomedin-C, LH, FSH, testosterone, estradiol, progesterone, T3, T4, TSH and cortisol were measured. Among those, the levels of plasma GH, PRL and somatomedin-C were high. Serum alkaline phosphatase was increased. OGTT did not suppress plasma OH concentration and GH showed paradoxical response to TRH and LHRH. GH was suppressed after a test-dose of somatastatin and bromocriptine. Brain MRI demonstrated a mass lesion in sella turcica and another mass lesions in nasal cavity and posterior occipital bone. Whole body bone scan revealed increased uptake in skull, nasal bone, both 9th posterior rib, both femurs, both tibias, left scapular and pelvic bone. These fmdings were consistent with bone tumor such as fibrous dysplasia. We report a case with incomplete MeCune-Albright syndrome including acromegaly, hyperprolactinemia and polyostotic fibrous dysplasia.

A Case of Piouitary Hyperplasia with Retardation due to Primary Hypothyroidism.: Hong Seung Kim, Choon Hee Chung, Young Goo Shin, Bong Ki Lee; J Korean Endocr Soc. 1997;12(4):589-595. Published online January 1, 2001

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Abstract PDF: Primary hypothyroidism can result in reactive enlargement of the pituitary gland which is indistinguishable from primary pituitary lesions in clinical presentation and on magnetic resonance imaging. A 17-year-old girl came to the hospital due to short stature, general weakness and galac-torrhea. The magnetic resonance imaging (MRI) study showed pitutary enlargement. The hormone study showed hyperprolactinemia, decreased basal growth hormone level and primary hypothyroi-dism. By thyroid replacement therapy only, mass was successfully regressed on follow up MRI after 4 months, and growth acceleration could be achieved.

A Case of Isolated ACTH Deficiency Accompanied by hyperprolactinemia.: Young Seung Kim, Gwang Il Kim, Dae Su Kim, Jeon Ok An, Sang Jeong Yoon, Hee Cheol Jang, Kang Seo Park; J Korean Endocr Soc. 1997;12(3):462-467. Published online January 1, 2001

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Abstract PDF: Isolated ACTH deficiency is a uncommon disorder causing secondary adrenocortical insufficiency. Less than 200 cases have been reported in the world. The major clinical manifestations are hypoglycemia, weight loss, hypotension, anemia, weakness, nausea, inability to excrete water load, and hyponatremia. A 56-year-old male was admitted because of weakness, fatigue, nausea and vomiting. He was pallor and not associated with hyperpigmentation. The basal plasma ACTH and cortisol levels were 8.30 pg/ml and 0.6 ug/dl. The serum cortisol did not response to rapid ACTH stimulation test. On combined pituitary stimulation test, the cortisol did not response to insulin-induced hypoglycemia. Other anterior pituitary hormones showed normal responses except elevated prolactin level. Six months after glucocorticoid replacement therapy, the elevated basal prolactin level returned to normal. Brain MRI did not show any anatomic abnormalities of the sellar and suprasella area. We report a case of isolated ACTH deficiency accompanied by hyperprolactineia, which respond to glucocorticoid replacement therapy.

Original Article

Clinical use of Urinary Androgen Metabolites in Hyperprolactinemia.: Kyoung Rae Kim, Sung Kil Lim, Young Duk Song, Hyun Chul Lee, Kap Bum Huh, Eun Sook Kim, Su Youn Nam, Eun Jig Lee, Bong Chul Jung, Byeong Kee Choi, Jae Ho Shin; J Korean Endocr Soc. 1997;12(3):443-449. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Hyperprolactinemia has been linked with hyperandrogenism and hirsutism in some women. High plasma Dihydroandrosterone and DHA-S levels were reported in patients with hyperprolactinemia and a dissociation of adrenal androgen and cortisol secretion occurs in normal subjects. The mechanism has not been elucidated, but it has been suggested that pituitary factors other than ACTH modulate adrenal androgen synthesis, One candidate hormone is prolactin. Adrenal tissue has been found to possess prolactin receptors and prolactin has been shown to act synergistically with ACTH and lowers the activity of the enzyme 5a-reductase or 3B-hydroxysteroid dehydrogenase (3B-HSD). The aim of this study was to investigate the secretion of adrenal androgen metabolites in patients with idiopathic hyperprolactinemia and prolactinoma and to deterrnine the relationship with prolactin and androgens. METHODS: We measured 24 hour-urinary DHEA, androstenedione, androsterone, pregnenolone, tetrahydrocorticoid and cortisol in 16 normal controls and 5 patients with idiopathic hyperprolac-tinemia (HP) and 12 patients with prolactonoma in the early follicular phase. RESULTS: Urinary DHEA, AD (androsteredione), and androsterone, the metabolites of adrenal androgen, were significantly higher in both patients with idiopathic HP and prolactinoma compared with those in normal controls (p<0.05), whereas they were not different in both disease groups. Urinary pregnenolone levels, early metabolite of adrenal steroid synthesis, were lower in patients. In contrast, urinary tetrahydorcortisol and cortisol were higher in patients compared to controls. There was no difference in DHEA:androsterone ratio between patients and controls. And there were no correlation between prolactin levels and the levels of androgenic metabolites or clinical symptoms. CONCLUSION: Prolactin has a tropic effct on the secretion of androgens and steroids by the adrenal cortex. But prolactin levels were not correlated with androgen levels or clinical symptoms (amenorrhea), and it might have little effect on lowering the activity of 3B-HSD.

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