Clinically functioning gonadotropin-secreting pituitary adenoma

in Endocrinology, Diabetes & Metabolism Case Reports
Authors:
Noor Alnasrallah Department of Internal Medicine, Adan Hospital, Kuwait

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https://orcid.org/0000-0003-4326-4041
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Khaled Aljenaee Department of Internal Medicine, Endocrine and diabetes division, Adan Hospital, Kuwait

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https://orcid.org/0000-0002-8609-2190
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Maryam AlMurshed Department of Laboratory Medicine, Anatomical Pathology/Neuropathology Division, Sabah Hospital, Kuwait

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Sulaiman Hajji Department of Internal Medicine, Endocrine and diabetes division, Adan Hospital, Kuwait

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Correspondence should be addressed to N AlNasrallah: Noor.A.AlNasrallah@gmail.com

*(N Alnasrallah is currently General Surgery Resident, University of British Columbia, Canada)

Open access

Summary

Gonadotroph adenomas are the most common type of nonfunctional pituitary adenomas. However, functioning gonadotroph adenomas causing clinical manifestations are rare. We present the case of a 42-year-old man with an incidental finding of a pituitary gland mass. A pituitary MRI revealed a 3 cm macroadenoma, and laboratory investigations revealed elevated follicle-stimulating hormone (FSH) and total testosterone levels. A diagnosis of functioning FSH-secreting pituitary adenoma was considered, with possible concomitant luteinizing hormone secretion, given the elevated testosterone, prompting further evaluation. Testicular ultrasound showed bilaterally enlarged testicles, and visual field testing revealed a monocular superior temporal defect. Transsphenoidal resection of pituitary adenoma was the treatment of choice. Histopathology assessment confirmed the diagnosis of gonadotroph-secreting adenoma, with positive staining for FSH. Within the 12-week postoperative period, FSH and testosterone levels normalized, and the patient experienced significant improvement in vision, along with the resolution of macroorchidism. While functional gonadotroph adenomas are rare, patients can present with a wide range of symptoms that are often unnoticeable due to their slow development. Careful evaluation can help guide multidisciplinary management to achieve full remission.

Learning points

  • Endocrine evaluation is indicated in all cases of pituitary incidentalomas to determine functional status.

  • Clinically functioning gonadotroph adenomas, while rare, pose a diagnostic challenge and require careful clinical evaluation.

  • Transsphenoidal surgery is the mainstay of treatment of functioning gonadotroph adenomas, with the involvement of a multidisciplinary team to achieve desirable outcomes.

Abstract

Summary

Gonadotroph adenomas are the most common type of nonfunctional pituitary adenomas. However, functioning gonadotroph adenomas causing clinical manifestations are rare. We present the case of a 42-year-old man with an incidental finding of a pituitary gland mass. A pituitary MRI revealed a 3 cm macroadenoma, and laboratory investigations revealed elevated follicle-stimulating hormone (FSH) and total testosterone levels. A diagnosis of functioning FSH-secreting pituitary adenoma was considered, with possible concomitant luteinizing hormone secretion, given the elevated testosterone, prompting further evaluation. Testicular ultrasound showed bilaterally enlarged testicles, and visual field testing revealed a monocular superior temporal defect. Transsphenoidal resection of pituitary adenoma was the treatment of choice. Histopathology assessment confirmed the diagnosis of gonadotroph-secreting adenoma, with positive staining for FSH. Within the 12-week postoperative period, FSH and testosterone levels normalized, and the patient experienced significant improvement in vision, along with the resolution of macroorchidism. While functional gonadotroph adenomas are rare, patients can present with a wide range of symptoms that are often unnoticeable due to their slow development. Careful evaluation can help guide multidisciplinary management to achieve full remission.

Learning points

  • Endocrine evaluation is indicated in all cases of pituitary incidentalomas to determine functional status.

  • Clinically functioning gonadotroph adenomas, while rare, pose a diagnostic challenge and require careful clinical evaluation.

  • Transsphenoidal surgery is the mainstay of treatment of functioning gonadotroph adenomas, with the involvement of a multidisciplinary team to achieve desirable outcomes.

Background

Pituitary adenomas are benign tumors that constitute 10–15% of all brain tumors. They can be either functioning or nonfunctioning, with most nonfunctioning pituitary adenomas being gonadotroph adenomas. Only a few cases were reported in the literature of functioning gonadotroph adenomas with a diverse range of clinical presentations. Herein, we present a case of an otherwise healthy middle-aged man with an incidental finding of a clinically functioning gonadotropin-secreting pituitary adenoma.

Case presentation

A 42-year-old male was admitted due to COVID-19 infection. Upon evaluation, he reported that he had a brain MRI performed a few years back in his country of origin. According to the patient, it revealed a brain mass that necessitated further investigation, which he did not follow up with; no records were available explaining why a brain MRI was obtained at that time. This piece of information prompted a thorough evaluation of the patient’s medical history. He first became aware of the brain mass 12 years ago when he was involved in a motor vehicle accident, and a CT brain scan was obtained at the time. Back then, he was informed that he had a small brain mass and that no urgent surgical intervention was needed. He reported experiencing blurred vision affecting only his right eye for the past few years, as well as dizziness. He elaborated that he would occasionally feel faint or lightheaded while performing his usual daily activities, and when he sought medical attention, he was informed that he had low blood pressure and was advised to consume salt/salty food to alleviate his dizziness. The dizziness was not related to posture. Otherwise, he did not report any history of headaches, seizures, or other visual deficits, and was generally in good health.

He is married and has two children, aged 10 and 2; he denied any sexual or fertility problems. He is a smoker (7–8 pack-years) but does not consume any alcohol. He does not take any medications regularly.

On examination, the patient had testicular enlargement, exceeding the maximum 25 cm3 measurement of the Prader orchidometer. Clinical assessment of the visual fields using the confrontational method revealed a defect of the temporal field vision affecting only the left eye. Regarding the COVID-19 diagnosis, the patient presented to the hospital with a fever, and a nasopharyngeal swab for SARS-CoV-2 PCR was obtained, yielding a positive result. The patient was admitted to the COVID-19 ward, where he was treated conservatively with antipyretics and supplemental oxygen; he did not receive steroids for treatment. Then, he was transferred to the medical ward for further evaluation of the pituitary adenoma.

Investigation

A pituitary MRI was performed, revealing a pituitary gland mass measuring 30 × 23 × 22 mm, expanding the pituitary fossa and extending to the suprasellar cistern (Fig. 1). Basic laboratory investigations and a full anterior pituitary hormonal profile were obtained, which revealed a low free T3 level at 1.8 pmol/L (normal range (NR): 3.1–6.8 pmol/L) and a low free T4 level at 6.6 pmol/L (NR: 12–22 pmol/L), with a normal TSH level at 3.54 mIU/L (NR: 0.27–4.2 mIU/L). Additionally, there was a high FSH level at 31.4 IU/L (NR: 1–18 IU/L) and a high total testosterone level at 50.31 nmol/L (NR: 8.3–32.9 nmol/L), with no other hormonal abnormality, and no erythrocytosis (Table 1).

Figure 1
Figure 1

A. Axial T1-weighted + GAD image. B. Sagittal T1-weighted + GAD image. C. Coronal T1-weighted + GAD image. Pituitary MRI displaying a 30 × 23 × 22 mm pituitary mass expanding the pituitary fossa and extending to suprasellar cistern. Suprasellar component of the lesion abutting the optic chiasm and circle of Willis arteries. Laterally on the left side, the lesion is abutting the lateral margin of the internal carotid artery within the cavernous sinus (grade I invasion). The right side of the lesion is reaching the lateral margin of intracavernous carotid artery (grade III invasion).

Citation: Endocrinology, Diabetes & Metabolism Case Reports 2024, 1; 10.1530/EDM-22-0322

Table 1

Hormonal profile.

Pre-op Post-op Normal values
6 weeks 12 weeks
LH (IU/L) 6.4 1.5 2.8 1.8–8.6
FSH (IU/L) 31.4 1.2 1.9 1–18
Testosterone (nmol/L) 50.31 0.66 11.3 8.3–32.9
Prolactin (mIU/L) 341.4 161.7 137.5 44.7–376.7
TSH (mIU/L) 3.540 2.090 6.31 0.27–4.2
Free T4 (pmol/L) 6.6 14.3 15 12–22
Morning cortisol (nmol/L) 274 296 410 171–536

Testicular ultrasound was performed (Fig. 2), revealing bilaterally enlarged testicles, with the right testis measuring 5.44 × 3.63 × 2.72 cm – 38.14 cm3 in volume and the left testis measuring 5.16 × 3.11 × 2.93 cm – 33.38 cm3 in volume (volume (cm3) = 0.71 × length × width × depth (cm)) (1).

Figure 2
Figure 2

Ultrasound of the scrotum for assessment of testicular size showing bilaterally enlarged testicles. A. Right testis measuring 5.44 × 3.63 × 2.72 cm – 38.14 cm3 volume; normal shape and echotexture, multiple calcific foci, no hydrocele. B. Left testis measuring 5.16 × 3.11 × 2.93 cm – 33.38 cm3 volume; normal shape and echotexture, multiple calcific foci, no hydrocele.

Citation: Endocrinology, Diabetes & Metabolism Case Reports 2024, 1; 10.1530/EDM-22-0322

Visual acuity testing was unremarkable. Visual Field testing, using a 30-2 Humphrey visual field (HVF) analyzer was performed and revealed a monocular superior temporal defect affecting the left eye. Right eye findings were normal.

Treatment

Based on the results of the hormonal profile, the patient was started on levothyroxine and hydrocortisone. Surgical intervention was delayed until two negative results of exit swabs for SARS-CoV-2.

The patient underwent transsphenoidal resection of the pituitary adenoma in July 2020. He did not receive glucocorticoids preoperatively despite borderline low cortisol levels but was monitored closely postoperatively. Histopathology assessment confirmed the diagnosis of gonadotroph-secreting adenoma, with positive immunostaining for FSH. Immunostaining was rare for LH and negative for ACTH, TSH, prolactin, and growth hormone (Fig. 3).

Figure 3
Figure 3

Histopathology of the pituitary tumor shows different growth patterns within the tumor, including nesting pattern (A), columns and cords (B), and rosette/papillary formation (C) (low power view). Tumor cells are monomorphic and show a chromophobic cytoplasm and a nucleus with stippled chromatin (D) (high power view). FSH immunostaining show strong cytoplasmic positivity in the majority of tumor cells (E). LH stain is scattered and patchy (F).

Citation: Endocrinology, Diabetes & Metabolism Case Reports 2024, 1; 10.1530/EDM-22-0322

No postoperative complications were reported. The patient was discharged on levothyroxine and hydrocortisone and scheduled for follow- up 6 weeks postoperatively for pituitary function assessment.

Outcome and follow-up

During the 6-week postoperative follow-up, basic laboratory investigations were repeated, as well as full anterior pituitary hormonal profile (Table 2), which revealed normalization of free T4 at 14.3 pmol/L (NR: 12–22 pmol/L) and a decrease in FSH to 1.2 IU/L (NR: 1–18 IU/L) and testosterone at 0.66 nmol/L (NR: 8.3–32.9 nmol/L). Morning cortisol levels on two occasions were indeterminate (270 nmol/L and 296 nmol/L respectively, NR: 171–536 nmol/L), so an insulin tolerance test (ITT) was performed to determine adrenal sufficiency (Table 2). Based on ITT findings, hydrocortisone was prescribed only for stressful conditions.

Table 2

Insulin tolerance test. Hypoglycemia was induced using six units of intravenous insulin (0.1 unit/kg). Patient remained asymptomatic at 30 min despite establishing hypoglycemia below 2.2 mmol/L, so test was continued until patient became symptomatic at 45 min. Hypoglycemia was reversed using 150 mL 20% dextrose.

Baseline 30 min 45 min 15 min post dextrose
Blood glucose* (mmol/L) 4.6 2.1 2.4 11.7
Cortisol (nmol/L) 382 417 451 410
ACTH (pg/mL) 65.10 175
GH (mIU/L) 0.05 0.06 0.16 0.25

*Determined by glucometer.

GH, growth hormone.

Assessment of visual acuity and visual field revealed marked improvement compared to the previous findings of left upper quadrantanopia affecting the left eye. The improvement was appreciated by the patient. Pituitary MRI was also repeated, with findings of enhancing soft tissue remnants manifested at the right-sided base of the pituitary fossa.

At 12 weeks post operation, the anterior pituitary hormonal profile (Table 2) revealed an elevation of TSH at 6.31 mIU/L (NR: 0.27–4.2 mIU/L), based on which levothyroxine was discontinued, and normalization of testosterone at 11.3 nmol/L (NR: 8.3–32.9 nmol/L). He continued to follow up with levels of TSH, which later normalized. Testicular ultrasound was repeated (Fig. 4), showing a marked decrease in testicular size, with the right testis measuring 4.14 × 3.21 × 1.9 cm – 17.93 cm3 in volume and the left testis measuring 4.72 × 2.96 × 2.13 cm – 21.13 cm3 in volume (volume (cm3) = 0.71 × length × width × depth (cm)) (1).

Figure 4
Figure 4

Ultrasound of the scrotum for assessment of testicular size showing normal size testicles. A. Right testis measuring 4.14 × 3.21 × 1.9 cm – 17.93 cm3 volume; normal shape and echotexture, multiple calcific foci, no hydrocele. B. Left testis measuring 4.72 × 2.96 × 2.13 cm – 21.13 cm3 volume; normal shape and echotexture, multiple calcific foci, no hydrocele.

Citation: Endocrinology, Diabetes & Metabolism Case Reports 2024, 1; 10.1530/EDM-22-0322

Discussion

Pituitary adenomas are benign tumors that constitute 10–15% of all brain tumors (2). They are classified based on their size, function, pathology, and morphological subtypes, as well as hormonal content. According to size, pituitary adenomas are divided into microadenomas (≤10 mm in diameter), macroadenomas (>10 mm in diameter), and giant adenomas (>40 mm in diameter), and they can be either functioning or nonfunctioning adenomas (2). The latter is determined by the tumor’s ability to excessively secrete certain hormones that, in turn, lead to clinical manifestations. The revised WHO 2017 classification divides pituitary adenomas based on their adenohypophysial cell lineage and immunohistochemical assessment of transcription factors (2).

Pituitary adenomas can present with neurological abnormalities and hypopituitarism due to compression of the tumor on adjacent tissue. Symptoms may include headaches, visual disturbances, symptoms of hyposecretion of pituitary hormones, as well as cranial nerve palsies in some cases (3). In the case of functional adenomas, patients can also present with symptoms of hormonal hypersecretion (4, 5). In many cases (22.4%) (6), such as in our case, pituitary adenomas are detected incidentally when radiological studies of the brain are conducted for other reasons (7).

The diagnostic approach to pituitary adenomas starts with a detailed evaluation of the patient’s clinical condition focusing on symptoms of pituitary function and covering all anterior pituitary axes (8). Pituitary MRI is the preferred imaging study for the evaluation of pituitary tumors, measurement of tumor size, and assessment of invasiveness. Assessment of pituitary function or presence of hormonal hypersecretion is indicated. Based on the size and extension of the adenoma, a detailed neuro-ophthalmological assessment is recommended, which in most cases would reveal bitemporal hemianopia due to compression of the optic chiasm (3, eight, 9). Lastly, post-resection immunohistochemical staining and transcription factor assessment are performed to determine the adenohypophysial-cell lineage and confirm the diagnosis and the subclassification of the tumor (10).

Gonadotroph adenomas are pituitary adenomas that are derived from the steroidogenic factor 1 (SF-1) cell lineage and are the most common subtype of non-functioning pituitary adenomas (NFPA) (10). In the case of NFPA, gonadotroph cells secrete monomer subunits of gonadotropins (FSH-beta, LH-beta, and/or alpha-subunit), which are biologically inactive at the level of gonads and do not lead to symptoms related to hormonal hypersecretion (11). Gonadotroph adenomas can also be biochemically silent, in which there would be no secretion of gonadotropins or their subunits. In the case of functioning gonadotroph adenoma (FGA), such as in our case, gonadotroph cells secrete bioactive intact gonadotropin heterodimers that would lead to inadequate stimulation of gonads and exhibition of symptoms related to the hypersecretion of FSH and/or LH (11). FGA is rare, and only a few cases have been reported in the literature. In those cases, patients reported symptoms such as menstrual irregularities, polycystic ovarian syndrome (PCOS), and/or ovarian hyperstimulation syndrome (OHS) in premenopausal women, macroorchidism, sexual or reproductive dysfunction, and hypogonadism in men, and precocious puberty in children. Despite the wide range of symptoms FGA can cause, they are typically not discovered until they become macroadenomas, as patients are usually investigated for other causes for their symptoms (12, 13).

The recommended management of FGA is transsphenoidal resection of the tumor, with preservation of normal pituitary tissue (13, 14). Hormonal irregularities relating to the functioning adenoma are expected to resolve postoperatively. Radiation therapy may be used in cases of postoperative residual mass from the tumor; however, dopamine agonists and somatostatin analogs were found to be ineffective in the treatment of FGA (13, 14). Resolution of hormonal abnormalities after the resection of the tumor is seen in up to 50% of patients (8). Improvement of visual fields has been reported as early as 1 week postoperatively and can continue for more than 6 months after transsphenoidal resection, with better outcome in cases of early surgical intervention (9). Reduction in testicular size has been reported in some cases within the first postoperative year (1, 4). Postoperative follow-up is critical to assess the resolution of hormonal irregularities and symptoms related to the compressive effect of the tumor, to detect any abnormalities in pituitary function resulting from surgical intervention, and manage accordingly, as well as to determine the presence of any residual tissue (8).

In conclusion, FGA is a rare entity of pituitary adenomas with a wide range of symptoms, despite which they are frequently detected incidentally as macroadenomas in imaging studies. A detailed review of the patient’s symptomatology and clinical evaluation can determine the investigations needed to establish a diagnosis. The final diagnosis should be confirmed postoperatively by histopathology. Transsphenoidal resection remains the recommended treatment approach for FGA with follow-up care to ensure a favorable outcome.

Declaration of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the case study reported.

Funding

This study did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.

Patient consent

Written informed consent was obtained from the patient for publication of the submitted article and accompanying images.

Author contribution statement

The case report was written by NA, the medical intern caring for the patient. The case was reviewed by KA and SH, who were responsible for the diagnosis, medical management, and continued care of the patient. MA is the pathologist who reviewed the pathology.

Acknowledgements

We thank Dr W Azab and Dr K Hanafy, the neurosurgeons responsible for the surgical management; Noor Basosa, the optometrist responsible for the visual field testing; and Dr Sameh Salah, Dr Maged Mohammad, Dr Hassan Abdulraheem, and Dr Tarek Alfarrah, who are the radiologists responsible for conducting and reporting the radiological investigations.

References

  • 1

    Dahlqvist P, Koskinen LOD, Brännström T, & Hägg E. Testicular enlargement in a patient with a FSH-secreting pituitary adenoma. Endocrine 2010 37 289293. (https://doi.org/10.1007/s12020-009-9302-z)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Chin SO. Epidemiology of Functioning Pituitary Adenomas. Endocrinology and Metabolism 2020 35 237242. (https://doi.org/10.3803/EnM.2020.35.2.237)

  • 3

    Ntali G, & Wass JA. Epidemiology, clinical presentation and diagnosis of non-functioning pituitary adenomas. Pituitary 2018 21 111118. (https://doi.org/10.1007/s11102-018-0869-3)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Helseltine D, White MC, Kendall-Taylor P, De Krester DM, & Kelly W. Testicular enlargement and elevated serum inhibin concentrations occur in patients with pituitary macroadenomas secreting follicle stimulating Hormine. Clinical Endocrinology 1989 31 411423. (https://doi.org/10.1111/j.1365-2265.1989.tb01265.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Thakkar A, Kannan S, Hamrahian A, Prayson RA, Weil RJ, & Faiman C. Testicular "hyperstimulation" syndrome: A case of functional gonadotropinoma. Case Reports in Endocrinology 2014 2014 Article ID 194716. (https://doi.org/10.1155/2014/194716)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge WE, Vance ML, & McCutcheon IE. The prevalence of pituitary adenomas: a systematic review. Cancer 2004 101 613619. (https://doi.org/10.1002/cncr.20412)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Chamoun R, Layfield L, & Couldwell WT. Gonadotroph adenoma with secondary hypersecretion of testosterone. World Neurosurgery 2013 80 900.e7900.11. (https://doi.org/10.1016/j.wneu.2012.11.069)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Molitch ME. Diagnosis and treatment of pituitary adenomas: a review. JAMA 2017 317 516524. (https://doi.org/10.1001/jama.2016.19699)

  • 9

    Dhasmana R, Nagpal RC, Sharma R, Bansal KK, & Bahadur H. Visual fields at presentation and after trans-sphenoidal resection of pituitary adenomas. Journal of Ophthalmic and Vision Research 2011 6 187191.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Nishioka H, & Inoshita N. New WHO classification of pituitary adenomas (4th ed.): assessment of pituitary transcription factors and the prognostic histological factors. Brain Tumor Pathology 2018 35 5 76 1. (https://doi.org/10.1007/s10014-017-0307-7)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Katznelson L, Alexander JM, & Klibanski A. Clinical review 45: Clinically nonfunctioning pituitary adenomas. Journal of Clinical Endocrinology and Metabolism 1993 76 10891094. (https://doi.org/10.1210/jcem.76.5.8496297)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Ntali G, Capatina C, Grossman A, & Karavitaki N. Clinical review: Functioning gonadotroph adenomas. Journal of Clinical Endocrinology and Metabolism 2014 99 44234433. (https://doi.org/10.1210/jc.2014-2362)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Cote DJ, Smith TR, Sandler CN, Gupta T, Bale TA, Bi WL, Dunn IF, De Girolami U, Woodmansee WW, Kaiser UB, et al.Functional gonadotroph adenomas: case series and report of literature. Neurosurgery 2016 79 823831. (https://doi.org/10.1227/NEU.0000000000001188)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Khazai B, Swerdloff RS, & Wang C. Follicle stimulating hormone and luteinizing hormone secreting tumors. Pituitary Disorders 2013. (https://doi.org/10.1002/9781118559406.ch11)

    • PubMed
    • Search Google Scholar
    • Export Citation

 

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  • Figure 1

    A. Axial T1-weighted + GAD image. B. Sagittal T1-weighted + GAD image. C. Coronal T1-weighted + GAD image. Pituitary MRI displaying a 30 × 23 × 22 mm pituitary mass expanding the pituitary fossa and extending to suprasellar cistern. Suprasellar component of the lesion abutting the optic chiasm and circle of Willis arteries. Laterally on the left side, the lesion is abutting the lateral margin of the internal carotid artery within the cavernous sinus (grade I invasion). The right side of the lesion is reaching the lateral margin of intracavernous carotid artery (grade III invasion).

  • Figure 2

    Ultrasound of the scrotum for assessment of testicular size showing bilaterally enlarged testicles. A. Right testis measuring 5.44 × 3.63 × 2.72 cm – 38.14 cm3 volume; normal shape and echotexture, multiple calcific foci, no hydrocele. B. Left testis measuring 5.16 × 3.11 × 2.93 cm – 33.38 cm3 volume; normal shape and echotexture, multiple calcific foci, no hydrocele.

  • Figure 3

    Histopathology of the pituitary tumor shows different growth patterns within the tumor, including nesting pattern (A), columns and cords (B), and rosette/papillary formation (C) (low power view). Tumor cells are monomorphic and show a chromophobic cytoplasm and a nucleus with stippled chromatin (D) (high power view). FSH immunostaining show strong cytoplasmic positivity in the majority of tumor cells (E). LH stain is scattered and patchy (F).

  • Figure 4

    Ultrasound of the scrotum for assessment of testicular size showing normal size testicles. A. Right testis measuring 4.14 × 3.21 × 1.9 cm – 17.93 cm3 volume; normal shape and echotexture, multiple calcific foci, no hydrocele. B. Left testis measuring 4.72 × 2.96 × 2.13 cm – 21.13 cm3 volume; normal shape and echotexture, multiple calcific foci, no hydrocele.

  • 1

    Dahlqvist P, Koskinen LOD, Brännström T, & Hägg E. Testicular enlargement in a patient with a FSH-secreting pituitary adenoma. Endocrine 2010 37 289293. (https://doi.org/10.1007/s12020-009-9302-z)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Chin SO. Epidemiology of Functioning Pituitary Adenomas. Endocrinology and Metabolism 2020 35 237242. (https://doi.org/10.3803/EnM.2020.35.2.237)

  • 3

    Ntali G, & Wass JA. Epidemiology, clinical presentation and diagnosis of non-functioning pituitary adenomas. Pituitary 2018 21 111118. (https://doi.org/10.1007/s11102-018-0869-3)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Helseltine D, White MC, Kendall-Taylor P, De Krester DM, & Kelly W. Testicular enlargement and elevated serum inhibin concentrations occur in patients with pituitary macroadenomas secreting follicle stimulating Hormine. Clinical Endocrinology 1989 31 411423. (https://doi.org/10.1111/j.1365-2265.1989.tb01265.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Thakkar A, Kannan S, Hamrahian A, Prayson RA, Weil RJ, & Faiman C. Testicular "hyperstimulation" syndrome: A case of functional gonadotropinoma. Case Reports in Endocrinology 2014 2014 Article ID 194716. (https://doi.org/10.1155/2014/194716)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge WE, Vance ML, & McCutcheon IE. The prevalence of pituitary adenomas: a systematic review. Cancer 2004 101 613619. (https://doi.org/10.1002/cncr.20412)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Chamoun R, Layfield L, & Couldwell WT. Gonadotroph adenoma with secondary hypersecretion of testosterone. World Neurosurgery 2013 80 900.e7900.11. (https://doi.org/10.1016/j.wneu.2012.11.069)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Molitch ME. Diagnosis and treatment of pituitary adenomas: a review. JAMA 2017 317 516524. (https://doi.org/10.1001/jama.2016.19699)

  • 9

    Dhasmana R, Nagpal RC, Sharma R, Bansal KK, & Bahadur H. Visual fields at presentation and after trans-sphenoidal resection of pituitary adenomas. Journal of Ophthalmic and Vision Research 2011 6 187191.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Nishioka H, & Inoshita N. New WHO classification of pituitary adenomas (4th ed.): assessment of pituitary transcription factors and the prognostic histological factors. Brain Tumor Pathology 2018 35 5 76 1. (https://doi.org/10.1007/s10014-017-0307-7)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Katznelson L, Alexander JM, & Klibanski A. Clinical review 45: Clinically nonfunctioning pituitary adenomas. Journal of Clinical Endocrinology and Metabolism 1993 76 10891094. (https://doi.org/10.1210/jcem.76.5.8496297)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Ntali G, Capatina C, Grossman A, & Karavitaki N. Clinical review: Functioning gonadotroph adenomas. Journal of Clinical Endocrinology and Metabolism 2014 99 44234433. (https://doi.org/10.1210/jc.2014-2362)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Cote DJ, Smith TR, Sandler CN, Gupta T, Bale TA, Bi WL, Dunn IF, De Girolami U, Woodmansee WW, Kaiser UB, et al.Functional gonadotroph adenomas: case series and report of literature. Neurosurgery 2016 79 823831. (https://doi.org/10.1227/NEU.0000000000001188)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Khazai B, Swerdloff RS, & Wang C. Follicle stimulating hormone and luteinizing hormone secreting tumors. Pituitary Disorders 2013. (https://doi.org/10.1002/9781118559406.ch11)

    • PubMed
    • Search Google Scholar
    • Export Citation