Medical Treatment and Surgical Indications for Functioning Pituitary Adenomas

AbstractPituitary adenomas represent approximately 15% of brain tumors; incidence is significantly on the increase due to widespread use of magnetic resonance imaging. Surgery remains the first-line treatment for most tumors overall. The role of dopaminergic agonists (DAs) and somatostatin receptor ligands (SRLs) in the treatment of pituitary adenomas is quite well established for prolactinomas and growth hormone (GH) excess. However, over the last decade new multi-receptor binding SRLs are increasingly used for treatment of acromegaly and Cushing’s disease. SRLs/DA chimeric compounds seem to have enhanced potency and efficacy when compared to that of individual SRLs or DA receptor agonists according to preclinical data. However, following negative results, more research is needed to determine if this interesting mechanism will translate into positive clinical effects for acromegaly patients. Furthermore, new agents that block adrenal steroidogenesis have been developed in phase III clinical trials for Cushing’s disease and several new compounds working at the pituitary level and/or blocking the glucocorticoid receptor are also in development. Combination therapy of drugs with similar or different mechanisms (possibly synergistic) are also on the increase. A growing awareness regarding all mechanisms involved in both control of pituitary secretion and cellular proliferation might allow for sole medical treatment of pituitary adenomas, especially macroadenomas, rather than surgery and/or radiation therapy, in the future. Moreover, the underlying decision on how to treat patients with pituitary adenomas should be individualized on a case-by-case basis with not only a goal of tumor shrinkage and biochemical control, but also of improving patients’ quality of life.

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Primary Medical Treatment of Thyrotropin–Secreting Pituitary Adenomas by First-Generation Somatostatin Analogs: A Case Study of Seven Patients

Thyroid ◽

10.1089/thy.2015.0041 ◽

2015 ◽

Vol 25 (8) ◽

pp. 877-882 ◽

Cited By ~ 14

Author(s):

Frédérique Rimareix ◽

Solange Grunenwald ◽

Delphine Vezzosi ◽

Louis-David Rivière ◽

Antoine Bennet ◽

...

Keyword(s):

Medical Treatment ◽

Pituitary Adenomas ◽

First Generation ◽

Somatostatin Analogs

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Thyrotropin-Secreting Pituitary Adenoma Successfully Treated With Cabergoline

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1977 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A967-A968

Author(s):

Aisha R Saand ◽

Monica Flores ◽

Sura Alqaisi ◽

Ossama Lashin

Keyword(s):

Pituitary Adenoma ◽

Medical Treatment ◽

Pituitary Adenomas ◽

Reference Range ◽

Clinical Manifestations ◽

Alternative Form ◽

Thyroid Function Tests ◽

Invasive Treatment ◽

Α Subunit

Abstract Background: Thyrotropin secreting pituitary adenomas (TSH-oma) account for less than 1% of pituitary adenomas and are a rare cause of hyperthyroidism. In this case, we describe the safe use of cabergoline with the subsequent achievement of euthyroid levels and the resolution of symptoms. Clinical Case: A 67-year-old female with a presumed history of hypothyroidism for the last 3 years managed with Armour thyroid was referred for fatigue associated with palpitations, intermittent diarrhea, insomnia, and anxiety. Her TSH was noted to be suppressed at that time, and her Amour thyroid was changed to Levothyroxine 25 mcg daily, which was eventually stopped as her symptoms persisted. Follow-up thyroid function tests (TFTs) showed elevated TSH (8.60 µU/mL, reference range 0.340 - 5.600 µU/mL), and elevated free T3 (10.8 pg/mL, reference range 2.7-4.7 pg/mL) and free T4 (2.0 ng/dL, reference range 0.8-1.5 ng/dL) levels. Further laboratory workup including basal prolactin, LH, FSH, hCG α-subunit, IGF-1, and ACTH levels were within the normal range. Physical examination showed diffuse thyroid enlargement. An I-123 thyroid uptake and scan showed uniform uptake throughout the gland with no focal hyperintense areas. A dedicated pituitary MRI was performed and revealed an 8 mm microadenoma in the posterior left adenohypophysis. The patient wanted to avoid any invasive treatment and refused trans-sphenoidal surgery and medical therapy was chosen. Unfortunately, using a somatostatin analog as part of the standard medical treatment was not an option due to the high cost and lack of insurance coverage. For these reasons, a trial of cabergoline was started to suppress TSH secretion. Atenolol 25 mg daily was added temporarily for the management of her sympathetic symptoms. On periodic follow-up, her symptoms gradually subsided, and TFTs remained within normal limits. Treatment was continued for one year. Conclusion: Clinical manifestations of hyperthyroidism with biochemical evidence of elevated thyroid hormone levels and TSH levels should raise a strong suspicion for central or secondary hyperthyroidism due to TSH secreting pituitary adenoma. Cabergoline might represent an effective alternative form of medical treatment for TSH-oma in certain situations where the first line therapeutic options are refractory, contraindicated, or declined.

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Clinically nonfunctioning pituitary tumours and gonadotropinomas

Oxford Textbook of Endocrinology and Diabetes ◽

10.1093/med/9780199235292.003.2158 ◽

2011 ◽

pp. 209-218 ◽

Cited By ~ 1

Author(s):

W. W. de Herder ◽

R. A. Feelders ◽

A. J. van der Lely

Keyword(s):

Medical Treatment ◽

Pituitary Adenomas ◽

Clinical Signs ◽

Signs And Symptoms ◽

Mass Effect ◽

Tumour Resection ◽

Ovarian Activity ◽

Pituitary Tumours ◽

Term Outcome ◽

Nonfunctioning Pituitary Adenomas

The significant progress that has been made in the past years in the medical treatment of all pituitary adenomas is in stark contrast with the lack of progress in the medical treatment of clinically nonfunctioning pituitary tumours, or adenomas. In fact, only secreting, or functioning, tumours can be treated by medical therapy with at least modest to very impressive effect. Clinically nonfunctioning pituitary adenomas do not produce clinical signs of hormonal hypersecretion. Therefore, signs and symptoms will depend on the mass effect of these adenomas over the central nervous system (1–3). Due to the lack of hypersecretion of hormones, nonfunctioning pituitary adenomas present themselves because of their mass effect and compression or destruction of surrounding tissues. This could also lead to hypopituitarism, which can be the presenting symptom as well (1–3). Despite their histologically benign nature, giant and ‘invasive’ nonfunctioning pituitary adenomas are one of the most complex neurosurgical challenges. Large nonfunctioning pituitary tumours are usually confined inferiorly by the sellar dura, superiorly by the elevated sellar diaphragm, and laterally by an intact medial wall of the cavernous sinus. If the anatomical extensions of the tumour are understood and a radical tumour resection is achieved, the visual and long-term outcome can be very rewarding. The goals of surgery are twofold: first to make a pathological diagnosis, and second, because these tumours are endocrinologically silent, to decompress the neural tissue (4). The vast majority of nonfunctioning pituitary adenomas are gonadotroph cell adenomas, as demonstrated by immunocytochemistry. However, they are rarely associated with increased levels of dimeric luteinizing hormone or follicle-stimulating hormone. Increased levels of subunits (free α‎-subunit mainly, LH-B subunit more rarely), however, are more frequently encountered, but are generally modest (5). In this chapter the term ‘clinically nonfunctioning pituitary adenomas’ is used to describe pituitary tumours, which in most instances produce low quantities of hormones causing no clinically recognizable symptomatology. In the few instances, in which such tumours produce intact gonadotropins that activate testicular or ovarian activity, the term ‘gonadotropinomas’ is used.

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3D Volumetric Measurements of GH Secreting Adenomas Correlate with Baseline Pituitary Function, Initial Surgery Success Rate, and Disease Control

Hormone and Metabolic Research ◽

10.1055/s-0043-107245 ◽

2017 ◽

Vol 49 (06) ◽

pp. 440-445 ◽

Cited By ~ 2

Author(s):

Amit Tirosh ◽

Georgios Papadakis ◽

Prashant Chittiboina ◽

Charalampos Lyssikatos ◽

Elena Belyavskaya ◽

...

Keyword(s):

Medical Treatment ◽

Disease Control ◽

Success Rate ◽

Pituitary Adenomas ◽

Volume Measurement ◽

Assessment Tools ◽

Oral Glucose ◽

Study Objective ◽

Initial Surgery ◽

Volumetric Measurements

AbstractThere is scarce data on the clinical utility of volume measurement for growth hormone (GH)-secreting pituitary adenomas. The current study objective was to assess the association between pituitary adenoma volumes and baseline endocrine evaluation, initial surgical success rate, and disease control among patients with acromegaly. A retrospective cohort study was conducted at a clinical research center including patients with acromegaly due to GH-secreting pituitary adenomas. Baseline hormonal evaluation and adenoma characteristics according to MRI were collected. Volumetric measurements of pituitary adenomas were performed using a semi-automated lesion segmentation and tumor-volume assessment tools. Rates of post-operative medical treatment, radiation therapy, and re-operation were gathered from the patients’ medical records. Twenty seven patients (11 females) were included, median age 21.0 years (interquartile range 29 years, range 3–61 years). Patients harboring adenomas with a volume <2 000 mm3 had higher chance to achieve disease remission [94.1% (n=16) vs. 50.0% (n=4), p<0.05]. Adenoma volumes positively correlated with baseline plasma GH levels before and after oral glucose administration, and with plasma IGF-I and PRL levels. Adenoma volume had negative correlation with morning plasma cortisol levels. Finally, patients harboring larger adenomas required 2nd surgery and/or medical treatment more often compared with subjects with smaller adenomas. Accurate 3D volume measurement of GH-secreting pituitary adenomas may be used for the prediction of initial surgery success and for disease control rates among patients with a GH-secreting pituitary adenomas and performs better than standard size assessments.

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Effects of Surgery on the 30-Day Survival Rate in Spontaneous Supratentorial Intracerebral Hemorrhage

Brain Sciences ◽

10.3390/brainsci11010005 ◽

2020 ◽

Vol 11 (1) ◽

pp. 5

Author(s):

Adrian Balasa ◽

Dana Ghiga ◽

Razvan-Sebastian Andone ◽

Ancuta Elena Zahan ◽

Ioan Alexandru Florian ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Medical Treatment ◽

Postoperative Mortality ◽

Severe Form ◽

Surgical Indications ◽

Group A ◽

Group B ◽

Gcs Score ◽

Postsurgical Outcomes ◽

The Relationship

Background: Spontaneous intracerebral hemorrhage (ICH) is a severe form of stroke. The efficacy of surgery as ICH treatment is controversial. We sought to compare the 30-day postoperative mortality rate between patients with surgically and medically treated ICH; Methods: This prospective study enrolled patients consecutively diagnosed with ICH and treated between 2017 and 2019. Patients meeting the study surgical indications were assigned to either surgical or medical treatment. The relationship between Glasgow Coma Scale (GCS) score, age, ICH location, ICH volume, and 30-day mortality was analyzed. Results: A total of 174 ICH patients were enrolled in this study. Of these, 136 met the surgery criteria; 65 of these underwent surgery (Group A), and 71 received medical treatment (Group B). Age and ICH location did not modify mortality. Although surgery did not overall improve mortality some better postsurgical outcomes were observed among patients surgically treated with GCS scores of at least 10 points and ICH volumes between 30 to 50 mL; Conclusions: Despite achieving an immediate reduction in intracranial pressure, surgery seems to be advantageous only for patients with ICH volumes between 30 to 50 mL and GCS scores of 10 points or higher;

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SSTR3 is a putative target for the medical treatment of gonadotroph adenomas of the pituitary

Endocrine Related Cancer ◽

10.1530/erc-14-0472 ◽

2014 ◽

Vol 22 (1) ◽

pp. 111-119 ◽

Cited By ~ 34

Author(s):

Misu Lee ◽

Amelie Lupp ◽

Nigel Mendoza ◽

Niamh Martin ◽

Rudi Beschorner ◽

...

Keyword(s):

Medical Treatment ◽

Pituitary Adenomas ◽

Somatostatin Receptor ◽

Somatostatin Analogs ◽

Putative Target ◽

Complete Surgical Resection ◽

Mrna And Protein Expression ◽

Low Levels ◽

Independent Cohort

Gonadotroph pituitary adenomas (GPAs) often present as invasive macroadenomas not amenable to complete surgical resection. Radiotherapy is the only post-operative option for patients with large invasive or recurrent lesions. No medical treatment is available for these patients. The somatostatin analogs (SSAs) octreotide and lanreotide that preferentially target somatostatin receptor type 2 (SSTR2) have little effect on GPAs. It is widely accepted that the expression of specific SSTR subtypes determines the response to SSAs. Given that previous studies on mRNA and protein expression of SSTRs in GPAs have generated conflicting results, we investigated the expression of SSTR2, SSTR3, and SSTR5 (the main targets of available SSAs) in a clinically and pathologically well-characterized cohort of 108 patients with GPAs. A total of 118 samples were examined by immunohistochemistry using validated and specific MABs. Matched primary and recurrent tissues were available for ten patients. The results obtained were validated in an independent cohort of 27 GPAs. We observed that SSTR3 was significantly more abundant than SSTR2 (P<0.0001) in GPAs, while full-length SSTR5 was only expressed in few tumors. Expression of SSTR3 was similar in primary and recurrent adenomas, was high in potentially aggressive lesions, and did not change significantly in adenomas that recurred after irradiation. In conclusion, low levels of expression of SSTR2 may account for the limited response of GPAs to octreotide and lanreotide. Given the potent anti-proliferative, pro-apoptotic, and anti-angiogenic activities of SSTR3, targeting this receptor with a multireceptor ligand SSA such as pasireotide may be indicated for potentially aggressive GPAs.

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Efficacy of Gamma Knife radiosurgery in the management of pituitary prolactinoma

Surgical Neurology International ◽

10.25259/sni_230_2021 ◽

2021 ◽

Vol 12 ◽

pp. 357

Author(s):

Bassam Mahmood Flamerz Arkawazi ◽

Ahmed Al Atraqchi ◽

Arjan Adnan ◽

Shaymaa Dheyab

Keyword(s):

Prospective Study ◽

Medical Treatment ◽

Contrast Enhancement ◽

Gamma Knife ◽

Pituitary Adenomas ◽

Hormone Level ◽

Gamma Knife Radiosurgery ◽

Intracranial Tumors ◽

Female Predominance ◽

Prolactin Hormone

Background: Gamma Knife radiosurgery (GKR) has been widely used in the management of a variety of intracranial tumors, including pituitary adenomas. Pituitary prolactinoma (Prs) is one of the most common types of these adenomas. Methods: This prospective study included 50 patients with pituitary Prs over a period from June 2017 to June 2018 at the Neurosciences Hospital, Baghdad/Iraq. The GKR procedure was performed using the Leksell Gamma Knife® Perfexion™, 192 beams of Cobalt 60 radiation were delivered through the intact skull to the pituitary Prs. Results: There is a significant female predominance 32 (72%). The results after 6 months of GKR showed significant improvement regarding the size of adenoma, prolactin hormone level, contrast enhancement on MRI, and medical treatment. Conclusion: The study showed that the GKR is a safe and effective modality of treatment in the management of pituitary Prs.

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GASTRO-ESOPHAGEAL REFLUX DISEASE: LIMITS OF MEDICAL TREATMENT AND SURGICAL INDICATIONS

Revista Española de Enfermedades Digestivas ◽

10.17235/reed.2020.7648/2020 ◽

2020 ◽

Author(s):

Antonio Ruiz de León San Juan ◽

Julio Pérez de la Serna Bueno ◽

María Concepción Sevilla Mantilla ◽

José Miguel Esteban López-Jamar ◽

Andrés Sánchez Pernaute

Keyword(s):

Medical Treatment ◽

Reflux Disease ◽

Esophageal Reflux ◽

Surgical Indications

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