Trans-sphenoidal surgery for microprolactinoma: an acceptable alternative to dopamine agonists?

AIMS: Reported cure rates following trans-sphenoidal surgery for microprolactinoma are variable and recurrence rates in some series are high. We wished to examine the cure rate of trans-sphenoidal surgery for microprolactinoma, and to assess the long-term complications and recurrence rate. DESIGN: A retrospective review of the outcome of trans-sphenoidal surgery for microprolactinoma, performed by a single neurosurgeon at a tertiary referral centre between 1976 and 1997. PATIENTS: All thirty-two patients operated on for microprolactinoma were female, with a mean age of 31 years (range 16-49). Indications for surgery were intolerance of dopamine agonists in ten (31%), resistance in six (19%) and resistance and intolerance in four (12.5%). Two patients were from countries where dopamine agonists were unavailable. RESULTS: The mean pre-operative prolactin level was 2933 mU/l (range 1125-6000). All but 1 had amenorrhoea or oligomenorrhoea, with galactorrhoea in 15 (46.9%). Twenty-five (78%) were cured by trans-sphenoidal surgery, as judged by a post-operative serum prolactin in the normal range. During a mean follow-up of 70 months (range 2 months to 16 years) there was one recurrence at 12 years. Post-operatively, one patient became LH deficient, two patients became cortisol deficient and two became TSH deficient. Out of 21 patients tested for post-operative growth hormone deficiency, 6 (28.6%) were deficient. Five patients developed post-operative diabetes insipidus which persisted for greater than 6 months. There were no other complications of surgery. The estimated cost of uncomplicated trans-sphenoidal surgery, and follow-up over 10 years, was similar to that of dopamine agonist therapy. CONCLUSION: In patients with hyperprolactinaemia due to a pituitary microprolactinoma, transsphenoidal surgery by an experienced pituitary surgeon should be considered as a potentially curative procedure. The cost of treatment over a 10 year period is similar in uncomplicated cases to long-term dopamine agonist therapy.

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Transsphenoidal surgery for prolactinomas: results and prognosis

Medicina ◽

10.3390/medicina43090089 ◽

2007 ◽

Vol 43 (9) ◽

pp. 691 ◽

Cited By ~ 2

Author(s):

Kęstutis Šinkūnas ◽

Daiva Rastenytė ◽

Vytenis Deltuva ◽

Robertas Knispelis ◽

Arimantas Tamašauskas

Keyword(s):

Surgical Treatment ◽

Dopamine Agonist ◽

Remission Rate ◽

Visual Field Defects ◽

Plasma Prolactin ◽

Long Term Outcomes ◽

Agonist Therapy ◽

Dopamine Agonist Therapy ◽

Younger Age

Objective. The aim of this study was to explore the long-term outcomes of surgery for transsphenoidal prolactinomas and the factors that influence them. Material and methods. Transsphenoidal approach for pituitary adenomas has been applied to 329 patients in the Department of Neurosurgery of Kaunas University of Medicine Hospital in the period of 1995 to 2006. Of these, 85 patients were operated for prolactinomas. Results. Of the 85 patients operated on for prolactinomas, 68 (80%) were females and 17 (20%) were males. Thirty-two microprolactinomas and 36 macroprolactinomas were diagnosed in women and 16 and 1, respectively, in men. Twenty (23.5%) patients (16 women and 4 men) had visual field defects before the operation. Dopamine agonist therapy was administered in 50 patients (38 women and 12 men) before the operation. Of 10 women, in whom microadenoma was diagnosed and no dopamine agonist therapy was prescribed, remission was achieved in 9 (90%) patients after the operation, while of 22 women, who was treated with dopamine agonists before the operation, remission was achieved only in 10 (45.5%) (P=0.01). Each year of age decreased the chance of remission by 8%. Conclusions. Remission after the surgical treatment was achieved in 11.8% of men and 47.1% of women hyperprowith prolactinomas. Remission rate was very high (90%) among women with microprolactinoma not treated with dopamine agonist before the surgical treatment. The probability of a good outcome of surgery among women with prolactinoma was related to younger age of the patient, noninvasive tumor growth, plasma prolactin level less than 2309 mU/L, and no use of dopamine agonist before the surgical treatment.

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Untreated Giant Macroprolactinoma with Chronic Cerebrospinal Fluid Leakage: An Unusual Complication

Case Reports in Endocrinology ◽

10.1155/2019/4825357 ◽

2019 ◽

Vol 2019 ◽

pp. 1-5

Author(s):

Mohamad Nazrulhisham Mad Naser ◽

Nor Azizah Aziz ◽

Noor Khairiah A. Karim

Keyword(s):

Cerebrospinal Fluid ◽

Dopamine Agonist ◽

Cerebrospinal Fluid Leak ◽

Serum Prolactin ◽

Cerebrospinal Fluid Leakage ◽

Unusual Complication ◽

Agonist Therapy ◽

Fluid Leakage ◽

Dopamine Agonist Therapy ◽

Fluid Leak

Macroprolactinoma has the potential to cause base of skull erosion and often extends into the sphenoid sinus. Rapid shrinkage of this invasive tumor following dopamine agonist therapy has been postulated to cause unplugging of the eroded area, leading to cerebrospinal fluid leakage. To the best of our knowledge, the occurrence of spontaneous cerebrospinal fluid leak in treatment-naive prolactinomas is very rare, the majority of which involve undiagnosed macroprolactinomas. We describe here a lady presented late with giant macroprolactinoma, complicated by cerebrospinal fluid leakage. This case raised the dilemma in the management pertaining to the role of either pharmacotherapy or surgical intervention, or combination of both. As she strictly refused surgery, she was treated with bromocriptine which was later changed to cabergoline. On follow-up, there was cessation of cerebrospinal fluid leak, marked reduction of serum prolactin level, and imaging evidence of tumor shrinkage. The majority of patients with medically induced cerebrospinal fluid leakage will require surgical procedures to overcome this complication; however, there are isolated cases of leakage resolution on continuing dopamine agonist therapy while awaiting surgery. The use of dopamine agonist does not necessarily cause worsening of cerebrospinal fluid leakage and instead may produce spontaneous resolution as in this case.

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The rapid diagnosis of sensitivity or resistance to dopamine agonists with depot bromocriptine

Acta Endocrinologica ◽

10.1530/acta.0.1160275 ◽

1987 ◽

Vol 116 (2) ◽

pp. 275-281 ◽

Cited By ~ 11

Author(s):

A. Grossman ◽

J. A. H. Wass ◽

M. Besser

Keyword(s):

Dopamine Agonists ◽

Oral Therapy ◽

Adverse Reactions ◽

Rapid Diagnosis ◽

Serum Prolactin ◽

Agonist Therapy ◽

Dopamine Infusion ◽

Dopamine Agonist Therapy ◽

Oral Doses ◽

Higher Doses

Abstract. Some patients with hyperprolactinaemia are unable to tolerate even low doses of oral bromocriptine. In such cases, it is difficult to predict whether serum prolactin might be normalized if higher doses could be tolerated, or whether true resistance to bromocriptine is present. We have investigated 8 such patients who were subjected to a dopamine infusion (4 μg/kg per min for 4 h), followed by an injection of 50 mg of depot bromocriptine on a separate occasion. Serum prolactin was normalized in 4 patients during dopamine, and in 6 patients 12–48 h following depot bromocriptine. The 2 patients who failed to respond to depot bromocriptine also failed to respond to high oral doses of bromocriptine, while the remaining 6 patients were successfully transferred to oral bromocriptine without adverse reactions after the depot preparation was administered, and with a normalization of serum prolactin. It is concluded that depot bromocriptine may represent a better predictor of true unresponsiveness to dopamine agonist therapy than a dopamine infusion, and may also allow for initiation onto oral therapy of previously intolerant patients.

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Delayed presentation of late-onset cerebrospinal fluid rhinorrhoea following dopamine agonist therapy for giant prolactinoma

Endocrinology Diabetes and Metabolism Case Reports ◽

10.1530/edm-14-0020 ◽

2014 ◽

Vol 2014 ◽

Cited By ~ 5

Author(s):

J K Prague ◽

C L Ward ◽

O G Mustafa ◽

B C Whitelaw ◽

A King ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Dopamine Agonist ◽

Surgical Repair ◽

Proliferation Index ◽

Serum Prolactin ◽

List Type ◽

Agonist Therapy ◽

Conventional Radiotherapy ◽

Dopamine Agonist Therapy ◽

Csf Rhinorrhoea

Summary Therapeutic shrinkage of prolactinomas with dopamine agonists achieves clinical benefit but can expose fistulae that have arisen as a result of bony erosion of the sella floor and anterior skull base by the invasive tumour, resulting in the potential development of cerebrospinal fluid (CSF) rhinorrhoea, meningitis, and rarely pneumocephalus. Onset of symptoms is typically within 4 months of commencing therapy. The management is typically surgical repair via an endoscopic transnasal transsphenoidal approach. A 23-year-old man presented to the Emergency Department with acute left limb weakness and intermittent headaches. Visual fields were full to confrontation. Immediate computed tomography and subsequent magnetic resonance imaging (MRI), demonstrated a 5 cm lobular/cystic mass invading the right cavernous sinus, displacing and compressing the midbrain, with destruction of the bony sella. He was referred to the regional pituitary multidisciplinary team (MDT). Serum prolactin was 159 455 mIU/l (7514.37 ng/ml) (normal ranges 100–410 mIU/l (4.72–19.34 ng/ml)). Cabergoline was commenced causing dramatic reduction in tumour size and resolution of neurological symptoms. Further dose titrations were required as the prolactin level plateaued and significant residual tumour remained. After 13 months of treatment, he developed continuous daily rhinorrhea, and on presenting to his general practitioner was referred to an otolaryngologist. When next seen in the routine regional pituitary clinic six-months later he was admitted for urgent surgical repair. Histology confirmed a prolactinoma with a low proliferation index of 2% (Ki-67 antibody). In view of partial cabergoline resistance he completed a course of conventional radiotherapy. Nine months after treatment the serum prolactin had fallen to 621 mIU/l, and 12 months after an MRI showed reduced tumour volume. Learning points CSF rhinorrhoea occurred 13 months after the initiation of cabergoline, suggesting a need for vigilance throughout therapy. Dedicated bony imaging should be reviewed early in the patient pathway to assess the potential risk of CSF rhinorrhoea after initiation of dopamine agonist therapy. There was a significant delay before this complication was brought to the attention of the regional pituitary MDT, with associated risk whilst left untreated. This demonstrates a need for patients and healthcare professionals to be educated about early recognition and management of this complication to facilitate timely and appropriate referral to the MDT for specialist advice and management. We changed our nurse-led patient education programme as a result of this case. Having developed partial cabergoline resistance and CSF rhinorrhoea, an excellent therapeutic response was achieved with conventional radiotherapy after limited surgery.

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526 Characteristics of Augmented RLS Patients on Dopamine Agonists at a Tertiary Referral Center: Where Do We Go From Here?

SLEEP ◽

10.1093/sleep/zsab072.525 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A207-A207

Author(s):

Jonathan Yeung Laiwah ◽

John Winkelman

Keyword(s):

Dopamine Agonist ◽

Dopamine Agonists ◽

Brain Research ◽

Transferrin Saturation ◽

Agonist Therapy ◽

Tertiary Referral ◽

Tertiary Referral Center ◽

Referral Center ◽

Dopamine Agonist Therapy ◽

Obstructive Sleep

Abstract Introduction Augmentation is a management dilemma in RLS patients on dopaminergic therapy. Understanding the clinical characteristics of such patients may assist in better management strategies. Methods Consecutive new consultations for RLS from 4/2016-6/2020 were identified from a single tertiary referral center in Boston, USA. Patients were included in this analysis if they had augmentation and current treatment with a dopamine agonist. Clinical information from initial consultation was collected. RLS severity at time of consultation was determined retrospectively with a modified IRLSSG severity score (0–12), assessing RLS symptom frequency (0–4), duration (0–4), and severity (0–4). Results Out of 209 referrals with RLS, 105 patients had augmentation, of whom 88 were on dopamine agonists at initial evaluation. Average age was 67 years (SD 11 years, range 39–88); 62 were female (59%). Mean duration of RLS symptoms was 27 years (SD 20), and 91% had symptoms > 10 years. Mean duration of dopamine agonist therapy was 11 years; 72% had previously been treated with pramipexole, 65% with ropinirole, 73% with rotigotine, and 16% with levodopa; 72% of patients had been treated with alpha-2-delta ligands, and 28% with opioids. Common comorbidities included obstructive sleep apnea (47%), obesity (49%), and depression (44%). Serotonergic medications were currently used by 25%. Of the 88 augmented patients on dopamine agonist therapy, 97% had earlier onset of symptoms and 33% had symptoms in both morning and afternoon; 53% reported anatomical extension. The mean modified IRLSSG score was 8.4 (SD 3.2). 66% of patients had either ferritin <75 mcg/L or transferrin saturation <20%. At the time of initial assessment, 49% were on pramipexole, 47% on rotigotine, 5% on rotigotine and 7% on levodopa: mean daily dopamine agonist dose was 1.23 mg (SD 1.20) of pramipexole equivalent. 37% were on alpha-2-delta ligands: mean daily dose 1014 mg (SD 830, median 700 mg) of gabapentin equivalent. Conclusion Higher than FDA-recommended dopamine agonist dosing and high prevalence of iron deficiency in patients with augmented RLS represent a treatment gap in the care of RLS patients in the community. Controlled studies of guideline-based therapy are indicated to determine optimal management of augmented RLS. Support (if any) Baszucki Brain Research Fund

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Long term tolerability of high dose ergoline derived dopamine agonist therapy for the treatment of Parkinson's disease

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp.73.5.602 ◽

2002 ◽

Vol 73 (5) ◽

pp. 602-603 ◽

Cited By ~ 8

Author(s):

P Navan

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dopamine Agonist ◽

High Dose ◽

Agonist Therapy ◽

Dopamine Agonist Therapy ◽

Term Tolerability

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Prolactinoma in a Male to Female Transgender Woman on Gender Affirming Hormone Therapy

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1617 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A795-A795

Author(s):

Leighton K Harned ◽

Rene J Harper

Keyword(s):

Pituitary Gland ◽

Hormone Therapy ◽

Dopamine Agonist ◽

Brain Mri ◽

Transgender Women ◽

Prolactin Secretion ◽

Reference Ranges ◽

Agonist Therapy ◽

Dopamine Agonist Therapy

Abstract Background: Estrogen promotes prolactin secretion and its role in prolactin secreting adenomas is still under investigation. The genesis and resolution of prolactinomas may be affected by gender affirming hormone therapy. Case Description: A 50 year old transgender female presented with new onset tunnel vision and extremity parathesias for one day. She had been taking oral estrogen for six years. Physical exam showed bilateral gynecomastia as well as galactorrhea. Her visual fields were intact by confrontation. Her brain MRI revealed a pituitary macroadenoma measuring 1.4cm x 1.3cm x 1.3cm. Laboratory studies showed prolactin 538 ng/mL (<20 ng/mL), IGF-1 89.0 (66-303 ng/ml). TSH 1.7 (0.4-4.7 mcIU/mL), Free T4 0.997 (0.58-1.76 ng/dL) and estradiol 103 pg/ml (N/A). She was treated with bromocriptine 5mg daily. Three months later galactorrhea had resolved, but gynecomastia was unchanged. The patient had a prolactin level of 3 ng/mL. Follow up brain MRI at one and three years showed no significant decrease in size of macroadenoma. Discussion: Despite this patient’s biochemical and symptomatic response to dopamine agonist therapy, her pituitary adenoma did not decrease in size over 3 years, which is a common occurrence with macroprolactinomas. However, her prolactin levels declined and her galactorrhea resolved with therapy. Research into the long term effects of gender transition therapy remains mainly in the realm of case reports and retrospective studies. Our review of the medical literature suggests that some transgender patients on estrogen therapy may have an increased risk of developing pituitary adenomas. However, guidelines have not yet been published and currently there are no recommendations for routine imaging or biochemical assessment during follow-up of these patients. While there are established reference ranges for prolactin levels for men, non-pregnant and pregnant women, no established reference ranges for prolactin levels are available for transgender women on gender affirming hormone therapy. Studies indicate that 76-86% of patients have a reduction in the size of their prolactinomas after dopamine agonist therapy. However, the same may not be true for transgender women on transfeminine hormone therapy with estrogen. Conclusion: Prolactinomas may commonly occur and be masked in transgender women on gender affirming hormone therapy due to the expected symptoms of gynecomastia, erectile dysfunction, and diminished libido from reduced testosterone levels. Estrogen promotes prolactin secretion by the pituitary gland and may have a role in development and expansion of prolactinomas. More research is needed in regards to the assessment and monitoring of the pituitary gland in transgender women on gender affirming hormone therapy with estrogen.

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