Covid-19 and pituitary apoplexy

Covid-19 and pituitary apoplexy

Kamel et al. reported a case of pituitary apoplexy associated with COVID-19 infection. Based on a patient’s clinical findings, review of the other reported cases, as well as the available literature, they put forth a multitude of pathophysiological mechanisms induced by COVID-19 that can possibly lead to the development of pituitary apoplexy. In their opinion, the association between both conditions is not just a mere coincidence. Although the histopathological features of pituitary apoplexy associated with COVID-19 are similar to pituitary apoplexy induced by other etiologies, future research may disclose unique pathological fingerprints of COVID-19 virus that explains its capability of inducing pituitary apoplexy 1).


A 75-year-old man who presented with a headache and was later diagnosed with hypopituitarism secondary to pituitary apoplexy. This occurred 1 month following a mild-to-moderate COVID-19 infection with no other risk factors commonly associated with pituitary apoplexy. This case, therefore, supplements an emerging evidence base supporting a link between COVID-19 and pituitary apoplexy 2).


Martinez-Perez et al. identified 3 consecutive cases of PA and concomitant COVID-19 infection. The most common symptoms at presentation were headache and vision changes. The included patients were successfully treated with surgical decompression and medical management of the associated endocrinopathy, ultimately experiencing improvement in their visual symptoms at the latest follow-up examination. COVID-19 infection in the perioperative period was corroborated by polymerase chain reaction test results in all the patients.

With the addition of our series to the literature, 10 cases of PA in the setting of COVID-19 infection have been confirmed. The present series was limited in its ability to draw conclusions about the relationship between these 2 entities. However, COVID-19 infection might represent a risk factor for the development of PA. Further studies are required. 3).


A review underlines that there could be a specific involvement of the pituitary gland which fits into a progressively shaping endocrine phenotype of COVID-19. Moreover, the care for pituitary diseases need to continue despite the restrictions due to the emergency. Several pituitary diseases, such as hypopituitarism and Cushing disease, or due to frequent comorbidities such as diabetes may be a risk factor for severe COVID-19 in affected patients. There is the urgent need to collect in international multicentric efforts data on all these aspects of the pituitary involvement in the pandemic in order to issue evidence driven recommendations for the management of pituitary patients in the persistent COVID-19 emergency. 4).


Pituitary apoplexy attributed solely to COVID-19 in the absence of other identifiable causes. While much remains to be discovered and understood regarding COVID-19, they discuss the potential pathophysiology of COVID-19-associated pituitary apoplexy and raise awareness of this clinical complication 5)


A neuro-ophthalmic presentation of pituitary apoplexy under the setting of COVID-19 infection in a middle-aged man who presented to ophthalmic emergency with sudden bilateral loss of vision along with a history of fever past 10 days. There was sluggishly reacting pupils and RT-PCR for COVID was positive. Imaging pointed the diagnosis as pituitary macroadenoma with apopexy. In view of pandemic situation, patient was given symptomatic treatment as per the protocols and stabilized. Vision also showed improvement to some extent and the patient is awaiting neurosurgery 6).


A case of a previously healthy woman with severe acute respiratory syndrome coronavirus 2 infection associated with pituitary apoplexy. The plausible pathophysiological mechanisms of pituitary apoplexy in infectious coronavirus disease 2019 are discussed. 7).


A 27-year-old male patient case with progressive decrease in visual acuity, associated with respiratory symptoms and intense headache. Multilobar infiltrate with a reticulonodular pattern is evident on chest CT scan. Brain CT scan with pituitary macroadenoma apoplexy was shown. SARS-Cov2 was confirmed, and respiratory support initiated. However, the patient died shortly afterward, secondary to pulmonary complications.

The angiotensin-converting enzyme (ACE) II receptor is expressed in circumventricular organs and in cerebrovascular endothelial cells, which play a role in vascular autoregulation and cerebral blood flow. For this reason, is rational the hypothesize that brain ACE II could be involved in COVID-19 infection. Underlying mechanisms require further elucidation in the future 8).


A 28-year-old G5P1 38w1d female presented with 4 days of blurry vision, left dilated pupil, and headache. She tested positive for SARS-CoV-2 on routine nasal swab testing but denied cough or fever. Endocrine testing demonstrated an elevated serum prolactin level, and central hypothyroidism. MRI showed a cystic-solid lesion with a fluid level in the pituitary fossa and expansion of the sella consistent with pituitary apoplexy. Her visual symptoms improved with corticosteroid administration and surgery was delayed to two weeks after her initial COVID-19 infection and to allow for safe delivery of the child. A vaginal delivery under epidural anesthetic occurred at 39 weeks. Two days later, transsphenoidal resection of the mass was performed under strict COVID-19 precautions including use of Powered Air Purifying Respirators (PAPRs) and limited OR personnel given high risk of infection during endonasal procedures. Pathology demonstrated a liquefied hemorrhagic mass suggestive of pituitary apoplexy. She made a full recovery and was discharged home two days after surgery.

They demonstrate the first known case of successful elective induction of vaginal delivery and transsphenoidal intervention in a near full term gravid patient presenting with pituitary apoplexy and acute SARS-CoV-2 infection. Further reports may help determine if there is a causal relationship or if these events are unrelated. Close adherence to guidelines for caregivers can greatly reduce risk of infection. 9).


A 25 year old male presented with dyspnoea, cough and high fevers for 4 days. He was commenced on broad-spectrum antimicrobials and oxygen therapy. His respiratory function deteriorated in spite of these measures and he required mechanical ventilation. CT showed left upper lobe consolidation as well as multifocal ground-glass opacification. Case 2: A 43 year-old male presented with headache and was found incidentally to have pneumonia. He was recently diagnosed with pituitary apoplexy secondary to an adenoma with resultant pituitary insufficiency but MRI brain was stable. His respiratory function deteriorated in spite of antibiotics and he required mechanical ventilation. CT showed likely atypical infection with resultant ARDS. Outcome Both underwent nasopharyngeal RT-PCR testing for SARS-CoV-2. Patient 2 was positive. Patient 1 was extubated and made a good recovery. Patient 2 was transferred to another centre for ECMO therapy. He died 27 days after transfer. Conclusion Given the atypical presentations in generally otherwise young and healthy individuals, the decision was made outside of national guidance to perform testing for SARS-CoV-2. This diagnosis had far-reaching implications for the SARS-CoV-2 pandemic within Ireland 10).


1)

Kamel WA, Najibullah M, Saleh MS, Azab WA. Coronavirus disease 2019 infection and pituitary apoplexy: A causal relation or just a coincidence? A case report and review of the literature. Surg Neurol Int. 2021 Jun 28;12:317. doi: 10.25259/SNI_401_2021. PMID: 34345458; PMCID: PMC8326077.
2)

Liew SY, Seese R, Shames A, Majumdar K. Apoplexy in a previously undiagnosed pituitary macroadenoma in the setting of recent COVID-19 infection. BMJ Case Rep. 2021 Jul 28;14(7):e243607. doi: 10.1136/bcr-2021-243607. PMID: 34321266; PMCID: PMC8319972.
3)

Martinez-Perez R, Kortz MW, Carroll BW, Duran D, Neill JS, Luzardo GD, Zachariah MA. Coronavirus Disease 2019 and Pituitary Apoplexy: A Single-Center Case Series and Review of the Literature. World Neurosurg. 2021 Aug;152:e678-e687. doi: 10.1016/j.wneu.2021.06.004. Epub 2021 Jun 12. PMID: 34129968; PMCID: PMC8196470.
4)

Frara S, Allora A, Castellino L, di Filippo L, Loli P, Giustina A. COVID-19 and the pituitary. Pituitary. 2021 Jun;24(3):465-481. doi: 10.1007/s11102-021-01148-1. Epub 2021 May 3. PMID: 33939057; PMCID: PMC8089131.
5)

Bordes SJ, Phang-Lyn S, Najera E, Borghei-Razavi H, Adada B. Pituitary Apoplexy Attributed to COVID-19 Infection in the Absence of an Underlying Macroadenoma or Other Identifiable Cause. Cureus. 2021 Feb 12;13(2):e13315. doi: 10.7759/cureus.13315. PMID: 33732566; PMCID: PMC7956048.
6)

Katti V, Ramamurthy LB, Kanakpur S, Shet SD, Dhoot M. Neuro-ophthalmic presentation of COVID-19 disease: A case report. Indian J Ophthalmol. 2021 Apr;69(4):992-994. doi: 10.4103/ijo.IJO_3321_20. PMID: 33727476; PMCID: PMC8012961.
7)

Ghosh R, Roy D, Roy D, Mandal A, Dutta A, Naga D, Benito-León J. A Rare Case of SARS-CoV-2 Infection Associated With Pituitary Apoplexy Without Comorbidities. J Endocr Soc. 2021 Jan 2;5(3):bvaa203. doi: 10.1210/jendso/bvaa203. PMID: 33501401; PMCID: PMC7798947.
8)

Solorio-Pineda S, Almendárez-Sánchez CA, Tafur-Grandett AA, Ramos-Martínez GA, Huato-Reyes R, Ruiz-Flores MI, Sosa-Najera A. Pituitary macroadenoma apoplexy in a severe acute respiratory syndrome-coronavirus-2-positive testing: Causal or casual? Surg Neurol Int. 2020 Sep 25;11:304. doi: 10.25259/SNI_305_2020. PMID: 33093981; PMCID: PMC7568102.
9)

Chan JL, Gregory KD, Smithson SS, Naqvi M, Mamelak AN. Pituitary apoplexy associated with acute COVID-19 infection and pregnancy. Pituitary. 2020 Dec;23(6):716-720. doi: 10.1007/s11102-020-01080-w. Epub 2020 Sep 11. PMID: 32915365; PMCID: PMC7484495.
10)

Faller E, Lapthorne S, Barry R, Shamile F, Salleh F, Doyle D, O’Halloran D, Prentice M, Sadlier C. The Presentation and Diagnosis of the First Known Community-Transmitted Case of SARS-CoV-2 in the Republic of Ireland. Ir Med J. 2020 May 7;113(5):78. PMID: 32603572.

Pituitary adenoma with gangliocytoma

Pituitary adenoma with gangliocytoma

AKA Mixed GangliocytomaPituitary Adenoma


Gangliocytomas originating in the sellar region are rare; most are tumors composed of gangliocytic and pituitary adenomatous elements, forming the so-called mixed gangliocytoma-pituitary adenoma. The majority of mixed gangliocytoma adenomas are associated with endocrinopathies, mainly acromegaly and less often Cushing disease and hyperprolactinemia.

Differentiating these mixed tumors from conventional pituitary adenomas can be difficult pre-operatively, and careful histological analysis after surgical resection is key to differentiating the two entities. There is little literature addressing the possible mechanisms for the development of mixed pituitary adenoma-gangliocytomas; however, several hypotheses have been proposed. It still remains unclear if these mixed tumors differ from a clinical perspective to pituitary adenomas; however, the additional neural component of the gangliocytoma does not appear to modify the aggressiveness or risk of recurrence after surgical resection. We report a unique case of acromegaly secondary to a mixed GH-secreting pituitary adenoma, co-existing with an intrasellar gangliocytoma.

Acromegaly due to a mixed GH-secreting pituitary adenoma and intrasellar gangliocytoma is rare. These mixed tumors cannot be distinguished easily from ordinary pituitary adenomas on the basis of clinical, endocrine or neuroradiologic findings, and histological analysis is required for a definitive diagnosis. Surgical resection is usually sufficient to provide a cure, without the need for adjuvant therapy. These mixed tumors appear to have a good prognosis although the natural history is not well defined 1).

The pathogenesis of these mixed tumors remains debatable, and ongoing research is required 2).

10 cases of mixed gangliocytoma and somatotroph adenomas were evaluated for patterns of cellular differentiation and expression of lineage-specific transcription factors. The tumors were characterized by immunohistochemistry for pituitary hormones, cytokeratins, Pit-1, and the neuronal markers NeuNneurofilaments (NFP), and MAP2. Double-labeling immunohistochemistry for Pit-1/GH, Pit-1/NFP, Pit-1/MAP2, and NeuN/GH was performed in 9/10 tumors. The data demonstrate that both adenomatous and ganglionic cells express the acidophilic lineage transcription factor Pit-1. Although mixed gangliocytomas and somatotroph adenomas show histologically distinct cellular populations, there is at least a small population of cells that coexpress the Pit-1 transcription factor and neuronal-associated cytoskeletal proteins favoring the theory of transdifferentiation of neuroendocrine cells into neuronal elements of these mixed tumors 3).

Although pituitary macroadenomas often cause mass effects on surrounding structures, it is extremely rare for pituitary lesions to disturb cerebrospinal fluid circulation. Sellar gangliocytoma-pituitary adenomas (SGPAs) (Pituitary adenoma with gangliocytoma) are also extremely rare.

Ryder et al., reported the unique case of a man with the unusual combination of acromegaly from an SGPA, who presented with unilateral hydrocephalus. A 60-year-old man presented with rapid neurological deterioration, bitemporal hemianopsia, and acromegalic features. Neuroimaging revealed a large sellar lesion extending superiorly into the left foramen of Monro, causing acute obstructive unilateral hydrocephalus. External ventricular drain placement improved consciousness immediately. The biochemical assessment confirmed acromegaly. Following transsphenoidal debulking, histology revealed a mixed gangliocytoma/sparsely-granulated somatotrophinoma. Despite the residual disease, his vision recovered remarkably, low-dose cabergoline controlled residual excess growth hormone (GH) secretion, and the residual tumour has remained extremely stable over 2 years. Hydrocephalus is an extremely rare complication of pituitary lesions, and unilateral hydrocephalus has never been reported previously. GH secretion in SGPAs is more common than for pituitary adenomas in general, raising questions regarding the aetiology and therapeutic approach to this rare combination tumour 4).


A 67-year-old woman with a past history of type 2 diabetes mellitus presented with worsening glycemic control. She had some acromegaly symptoms and magnetic resonance imaging demonstrated a pituitary tumor. Endocrinological examination found the resting growth hormone (GH) level within the normal range, but elevated insulin-like growth factor 1 level. A 75 g oral glucose tolerance test showed inadequate suppression of nadir GH levels. Acromegaly due to GH-secreting pituitary tumor was diagnosed. The patient underwent endoscopic transsphenoidal surgery resulting in gross total removal of the tumor and recovered well postoperatively. Histological examination of the tumor showed coexistence of relatively large gangliocytoma cells and pituitary adenoma cells, suggesting mixed gangliocytoma-pituitary adenoma. In addition, colocalization of GH and GH-releasing hormone (GHRH) in pituitary adenoma cells was revealed, so the adenomatous components were more likely to produce GHRH in our mixed gangliocytoma-pituitary adenoma case. Mixed gangliocytoma-pituitary adenoma is very rare, and the present unique case demonstrated only the adenomatous components associated with GHRH production.

Sellar gangliocytoma coexisting with pituitary adenoma is recognized as a mixed gangliocytoma-pituitary adenoma and is very rare. A proposed developmental mechanism of growth hormone (GH)-secreting mixed gangliocytoma-pituitary adenoma involves GH-releasing hormone (GHRH) produced by the gangliocytic components promoting the growth of tumor including GH-secreting adenomatous components. Since the present case indicated that the adenomatous components of mixed gangliocytoma-pituitary adenoma could secrete both GH and GHRH simultaneously, progression of GH-secreting mixed gangliocytoma and pituitary adenoma may involve exposure to spontaneously produced GHRH due to the adenomatous components 5).


Two 47-year-old females who presented with masses in the sellar region following a general examination and radiological imaging. The two patients underwent sellar region tumor resection via the trans-naso-sphenoid approach. The histopathological examination confirmed the diagnosis of a hormone-free pituitary adenoma with gangliocytoma. The two patients were in good condition and experienced no specific discomfort subsequent to the follow-up after surgery. Gangliocytoma is a slowly growing and non-metastasizing tumor. A biopsy is required to differentiate a gangliocytoma from a malignant neuroblastoma, and excision is usually curative 6).


Three cases of a composite sellar tumor composed of a gangliocytoma and an adenoma are presented. Two patients who showed acromegaly and hyperprolactinemia had a gangliocytoma and a growth hormone (GH)-prolactin cell adenoma in close proximity. The gangliocytoma contained growth hormone-releasing hormone (GHRH) by immunohistochemistry. At the electron microscopical level, the gangliocytoma was characterized by numerous synaptic vesicles. The third patient, a child with Cushing’s disease, presented a corticotropin-releasing hormone (CRH)-positive gangliocytoma in close contact with an adrenocorticotropic hormone (ACTH) secreting adenoma, the latter a typical densely granulated ACTH cell adenoma. Ultrastructurally, the gangliocytoma revealed synaptic vesicles and sparse secretory granules. The results suggest that gangliocytomas may promote the development of pituitary adenomas by hypersecretion of releasing hormones. Whereas 20 cases of sellar GHRH producing gangliocytomas in acromegaly are reported in the literature, the combination of a CRH-positive gangliocytoma and an ACTH cell adenoma in Cushing’s disease is apparently the first case 7).


1) , 2)

Lee MH, McKelvie P, Krishnamurthy B, Wang YY, Caputo C. An intrasellar pituitary adenoma-gangliocytoma presenting as acromegaly. Endocrinol Diabetes Metab Case Rep. 2017 Apr 27;2017:17-0035. doi: 10.1530/EDM-17-0035. PMID: 28469929; PMCID: PMC5409941.
3)

Lopes MB, Sloan E, Polder J. Mixed Gangliocytoma-Pituitary Adenoma: Insights on the Pathogenesis of a Rare Sellar Tumor. Am J Surg Pathol. 2017 May;41(5):586-595. doi: 10.1097/PAS.0000000000000806. PMID: 28079576.
4)

Ryder S, Robusto J, Robertson T, Alexander H, Duncan EL. Unilateral hydrocephalus from a gangliocytoma-somatotrophinoma: first reported case. Endocrinol Diabetes Metab Case Rep. 2021 Jul 1;2021:EDM210037. doi: 10.1530/EDM-21-0037. Epub ahead of print. PMID: 34236040.
5)

Teramoto S, Tange Y, Ishii H, Goto H, Ogino I, Arai H. Mixed gangliocytoma-pituitary adenoma containing GH and GHRH co-secreting adenoma cells. Endocrinol Diabetes Metab Case Rep. 2019 Oct 3;2019:19-0099. doi: 10.1530/EDM-19-0099. Epub ahead of print. PMID: 31581122; PMCID: PMC6790896.
6)

Chen D, Xu J, Zhong P, Huang X, Xu M. Pituitary adenoma with gangliocytoma: Report of two cases. Oncol Lett. 2014 Aug;8(2):781-784. doi: 10.3892/ol.2014.2183. Epub 2014 May 27. PMID: 25013498; PMCID: PMC4081391.
7)

Saeger W, Puchner MJ, Lüdecke DK. Combined sellar gangliocytoma and pituitary adenoma in acromegaly or Cushing’s disease. A report of 3 cases. Virchows Arch. 1994;425(1):93-9. doi: 10.1007/BF00193956. PMID: 7921420.

Pituitary adenoma classification

Pituitary adenoma classification

They are classified based on size or cell of origin. Pituitary adenoma can be described as microadenomamacroadenoma, and giant tumors based on size. Microadenoma is tumors less than 10 mm, while macroadenoma includes tumors larger than 10mm. Giant pituitary adenomas are more than 40 mm. There are functional pituitary adenomas in which the cell type that composes them causes increased secretion of one or multiple hormones of the anterior pituitary. Alternatively, there are Non-Functioning Pituitary Adenomas that do not secrete hormones, but they can compress the surrounding areas of the anterior pituitary leading to hormonal deficiencies 1).

see The 2017 World Health Organization classification of tumors of the pituitary gland.

In the fourth edition of the World Health Organization classification of endocrine tumors, are two critical changes to the classification for pituitary adenomas.

One is that the term “atypical adenoma,” which was characterized based on highly proliferative properties to predict adenomas that carry a poor prognosis, was completely eliminated due to the lack of definitive evidence. The other change is the introduction of more precise cell lineage-based classification of pituitary adenoma that is defined based on lineage-specific transcription factors and hormones produced. Accordingly, null cell adenomas have been re-defined as those that show completely negative immunostaining either for hormones or for adenohypophyseal transcription factors 2).

Somatotroph adenoma.

Lactotroph adenoma.

Tyrotroph adenoma.

Corticotroph adenoma.

Gonadotroph adenoma.

Null cell adenoma

Plurihormonal pituitary adenoma and double adenomas.


The classification is based upon the size, invasion of adjacent structures, sporadic or familial cases, biochemical activity, clinical manifestations, morphological characteristics, response to treatment, and recurrence 3).

Current classification systems for PAs are based primarily on secretory characteristics of the tumor but are also classified on the basis of phenotypical characteristics, including tumor size, degree of invasiveness (e.g., Knosp grade), and immunohistological findings 4).

The anterior WHO classification system for PAs was refined to include designations for benign adenoma, atypical adenoma, and pituitary carcinoma on the basis of p53 immunoreactivity, MIB-1 indexmitotic activity, and the absence/presence of metastases 5) 6).

These tumor types can be microadenomas or macroadenomas and can either be functional or non-functional.

By Size

Pituitary microadenoma

Pituitary macroadenoma

Giant pituitary adenoma

Volume can be calculated using MRI-guided volumetrics and an ellipsoid approximation (TV × AP × CC/2) transverse (TV), antero-posterior (AP) and cranio-caudal (CC).

By Function

Functioning pituitary adenoma

Nonfunctioning pituitary adenoma

Pituitary adenomas with gangliocytic component are rare tumors of the sellar region that are composed of pituitary adenoma cells and a ganglion cell component. Their histogenesis and hence nosology is not yet resolved because of the small number of cases reported and lack of large series in the literature 7).

Invasive pituitary adenomas and pituitary carcinomas are clinically indistinguishable until the identification of metastases.

Consistency

Although most authors differentiate easily aspirated (soft) tumors from those that are not (fibrous, might require prior fragmentation), there is no universally accepted PA consistency classification. Fibrous PA tends to be hypointense on T2WI and has lower apparent diffusion coefficient (ADC) values. Fibrous tumors seemed to present higher invasion into neighboring structures, including the cavernous sinus. Several articles suggest that dopamine agonists could increase PA consistency and that prior surgery and radiotherapy also make PA more fibrous. The anatomopathological studies identify collagen as being mainly responsible for fibrous consistency of adenomas.

Conclusions: Preoperative knowledge of PA consistency affords the neurosurgeon substantial benefit, which clearly appears to be relevant to surgical planning, risks, and surgery outcomes. It could also encourage the centralization of these high complexity tumors in reference centers. Further studies may be enhanced by applying standard consistency classification of the PA and analyzing a more extensive and prospective series of fibrous PA. 8).

Knosp Grade.

Hardy’s Classification of Pituitary Adenomas.


1)

Russ S, Shafiq I. Pituitary Adenoma. 2020 Feb 4. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK554451/ PubMed PMID: 32119338.
2)

Inoshita N, Nishioka H. The 2017 WHO classification of pituitary adenoma: overview and comments. Brain Tumor Pathol. 2018 Apr;35(2):51-56. doi: 10.1007/s10014-018-0314-3. Epub 2018 Apr 23. Review. PubMed PMID: 29687298.
3)

Syro LV, Rotondo F, Ramirez A, Di Ieva A, Sav MA, Restrepo LM, Serna CA, Kovacs K. Progress in the Diagnosis and Classification of Pituitary Adenomas. Front Endocrinol (Lausanne). 2015 Jun 12;6:97. doi: 10.3389/fendo.2015.00097. eCollection 2015. Review. PubMed PMID: 26124750; PubMed Central PMCID: PMC4464221.
4)

Knosp E, Steiner E, Kitz K, Matula C: Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings. Neurosurgery 33:610–618, 1993
5)

Barnes L, Eveson JW, Reichart P, David Sidransky: World Health Organization Classification of Tumours: Pathology and Genetics of Head and Neck Tumours Lyon, IARC Press, 2005
6)

Zada G, Woodmansee WW, Ramkissoon S, Amadio J, Nose V, Laws ER Jr: Atypical pituitary adenomas: incidence, clinical characteristics, and implications. J Neurosurg 114:336–344, 2011
7)

Balci S, Saglam A, Oruckaptan H, Erbas T, Soylemezoglu F. Pituitary adenoma with gangliocytic component: report of 5 cases with focus on immunoprofile of gangliocytic component. Pituitary. 2014 Jan 16. [Epub ahead of print] PubMed PMID: 24430434.
8)

Acitores Cancela A, Rodríguez Berrocal V, Pian H, Martínez San Millán JS, Díez JJ, Iglesias P. Clinical relevance of tumor consistency in pituitary adenoma. Hormones (Athens). 2021 Jun 19. doi: 10.1007/s42000-021-00302-5. Epub ahead of print. PMID: 34148222.
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