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Clinical manifestations and diagnosis of gonadotroph and other clinically nonfunctioning pituitary adenomas

Clinical manifestations and diagnosis of gonadotroph and other clinically nonfunctioning pituitary adenomas
Author:
Peter J Snyder, MD
Section Editor:
David S Cooper, MD
Deputy Editor:
Kathryn A Martin, MD
Literature review current through: Sep 2023.
This topic last updated: Apr 26, 2022.

INTRODUCTION — Most patients with pituitary adenomas present with signs and symptoms of hormone hypersecretion (eg, hyperprolactinemia, growth hormone [GH] excess, or hypercortisolism). However, 25 to 35 percent of pituitary adenomas are clinically nonfunctioning or "silent"; 70 to 90 percent of these are gonadotroph adenomas, making them the most common type of pituitary macroadenoma. Patients with clinically nonfunctioning adenomas most often present with neurologic symptoms due to mass effects, while others may be completely asymptomatic and be first detected on an imaging study done for reasons other than pituitary symptoms or disease. By the time patients present, a high percentage have biochemical evidence of hypopituitarism due to compression of normal pituitary cells by the macroadenoma.

The clinical features, evaluation, and diagnosis of clinically nonfunctioning pituitary adenomas are reviewed here. The treatment of these tumors and an overview of incidentally discovered sellar masses (pituitary incidentalomas) are discussed separately. (See "Treatment of gonadotroph and other clinically nonfunctioning adenomas" and "Pituitary incidentalomas".)

OVERVIEW OF PITUITARY ADENOMAS — Pituitary adenomas are classified by their cell of origin (lactotroph, gonadotroph, somatotroph, corticotroph, and thyrotroph) and their size (microadenomas <1 cm, macroadenomas ≥1 cm). Most adenomas (65 to 70 percent) secrete an excess amount of hormone including prolactin, growth hormone (GH), corticotropin (ACTH), or thyroid-stimulating hormone (TSH). (See "Causes of hyperprolactinemia" and "Causes and clinical manifestations of acromegaly" and "Causes and pathophysiology of Cushing syndrome" and "TSH-secreting pituitary adenomas".)

The remainder of pituitary adenomas (25 to 35 percent) are clinically nonfunctioning or "silent." Of these, 70 to 90 percent are gonadotroph adenomas [1]. There are also clinically nonfunctioning somatotroph [2,3], corticotroph, and lactotroph adenomas [4], although these are less common.

The majority of gonadotroph adenomas are clinically "silent" and difficult to identify because they are poorly differentiated and produce and secrete hormones inefficiently. The gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), consist of a common alpha subunit and a unique beta subunit. TSH and human chorionic gonadotropin (hCG) also consist of the common alpha subunit and a unique beta subunit. The hormones secreted by gonadotroph adenomas in order of decreasing frequency include: FSH, FSH-beta, alpha subunit, LH, and LH-beta [5].

Alpha subunit is not biologically active and also does not result in a clinical symptom due to its secretion. However, it is measured to evaluate patients with sellar masses to determine if the mass is pituitary in origin and whether there is accompanying hormonal hypersecretion. (See 'Hormone excess' below.)

EPIDEMIOLOGY — Estimates of the prevalence of pituitary adenomas are variable and are often based upon autopsy or magnetic resonance imaging (MRI) series. In a report from a single community of over 80,000 inhabitants in England, the prevalence of nonfunctioning pituitary adenomas (that had come to the attention of a clinician) was 22 per 100,000 [6]. This is likely an underestimate of the true prevalence, as many nonfunctioning pituitary adenomas go undiagnosed until they are very large or are identified on an imaging study done for unrelated reasons.

Gonadotroph adenomas are thought to be most common in men over age 50 years [1] and less common in similar aged women, but this could be due to difficulty in recognizing gonadotroph adenomas in this population. High serum gonadotropins would be unlikely to raise suspicion for a gonadotroph adenoma in a woman over 50 years since she is likely to have elevated basal serum gonadotropin concentrations from the normal menopause [7]. (See "Clinical manifestations and diagnosis of menopause".)

PATHOGENESIS — Gonadotroph adenomas, like other pituitary adenomas, appear to be true clonal neoplasms [8,9], but the mutations that cause them are not known. Genes that have been found to be overexpressed include the pituitary tumor transforming gene, Ki-67, and FGF-R [10-12]. The maternally-expressed gene 3 (MEG3) is underexpressed [13].

CLINICAL PRESENTATIONS — Nonfunctioning pituitary adenomas (including the majority of gonadotroph adenomas) are difficult to recognize clinically until they are large enough to cause symptoms due to a mass effect. The three most common presentations include the following (table 1) [14]:

Neurologic symptoms – Most commonly, visual symptoms; less commonly, headache

A pituitary mass that is discovered as an incidental finding when an imaging procedure is done for reasons other than pituitary symptoms or disease

Pituitary hypofunction due to compression of normal pituitary tissue by the adenoma

Less commonly, patients with gonadotroph adenomas may present with clinical syndromes due to hypersecretion of follicle-stimulating hormone (FSH) or, rarely, luteinizing hormone (LH; ovarian hyperstimulation or precocious puberty). (See 'Hormone excess' below.)

Neurologic symptoms

Visual impairment — Impaired vision, caused by suprasellar extension of the adenoma that compresses the optic chiasm, is the most common symptom that leads a patient with a gonadotroph or other clinically nonfunctioning adenoma to seek medical attention (image 1) [14-16].

The most common type of vision impairment is visual field loss, typically diminished vision in the temporal fields (superior temporal quadrantanopsia or temporal hemianopsia). One or both eyes may be affected. In a review of eight series of 1719 patients with clinically nonfunctioning pituitary adenomas, visual field disturbances were present in 798 (46 percent) [14], while in a single-center series of 295 patients, the frequency was even higher (192 of 295, 65 percent) [15].

Diminished visual acuity, which occurs when the optic chiasm is more severely compressed [16], was reported in approximately 30 percent of patients in one series [15]. Thus, an intrasellar lesion should be suspected when there is any unexplained pattern of visual loss.

The onset of visual deficits is usually so gradual that many patients do not seek ophthalmologic consultation for months or even years.

Diplopia, induced by oculomotor nerve compression resulting from lateral extension of the adenoma, may occur, but it is less common, occurring in up to 10 to 15 percent of patients in several large series [14].

Headache — Headaches, the second most common neurologic symptom, occur in 30 to 40 percent of patients [14,15] and are thought to be due to sellar expansion. There is no distinguishing characteristic of the headaches, although they are usually diffuse.

Other — Other less common neurologic symptoms include [16]:

Cerebrospinal fluid rhinorrhea, caused by inferior extension of the adenoma, rarely occurs spontaneously [17].

Pituitary apoplexy (sudden hemorrhage into a pituitary macroadenoma), is also rare. It causes excruciating headache and visual impairment [18]. This may occur spontaneously but has also been reported during pregnancy, surgery, and with anticoagulant use [19]. It has been described less commonly after thyrotropin-releasing hormone (TRH) and gonadotropin-releasing hormone (GnRH) stimulation tests [20,21] and with gonadotropin-releasing hormone (GnRH) agonist therapy for prostate cancer [22,23].

Incidental finding on imaging — The common use of magnetic resonance imaging (MRI) to evaluate symptoms in the head or neck has resulted in the incidental discovery of many intrasellar lesions. In two MRI series of 100 [24] and 52 [25] normal volunteers, 10 (10 percent) and 25 (38 percent), respectively, had previously unsuspected sellar lesions, but almost all were <10 mm. However, in one review of eight series of pituitary "incidentalomas" discovered on MRI, 68 percent were macroadenomas [14]. This percentage is much higher than other imaging series, suggesting that patients likely had symptoms suggestive of a sellar mass that led to the imaging study.

The evaluation and management of these adenomas are reviewed separately. (See "Pituitary incidentalomas".)

Symptoms due to hormonal abnormalities — Clinically nonfunctioning adenomas often present with evidence of hypopituitarism (usually biochemical). On rare occasions, gonadotroph adenomas present with hormonal hypersecretion causing a clinical syndrome such as ovarian hyperstimulation or precocious puberty.

Gonadotroph adenomas, like all other types of pituitary adenomas, can occur as part of the multiple endocrine neoplasia type 1 (MEN1) syndrome, a rare heritable disorder classically characterized by a predisposition to tumors of the parathyroid glands, anterior pituitary, and pancreatic islet cells. (See "Multiple endocrine neoplasia type 1: Genetics", section on 'MEN1 gene'.)

Hormone deficiencies — Patients who present with neurologic symptoms, when carefully questioned, may acknowledge symptoms of pituitary hormone deficiencies that are due to compression of nonadenomatous cells by the macroadenoma. However, these symptoms tend to be nonspecific (fatigue and lethargy) and are not usually the reason that the patient seeks medical attention.

The most common clinical hormone deficiency is impaired secretion of gonadotropins resulting in hypogonadism. In a series of 295 patients with nonfunctioning pituitary adenomas, 61 of 161 men (38 percent) had low serum gonadotropins, resulting in low serum testosterone, decreased libido, and erectile dysfunction [15]. In the same report, 33 percent of the women of reproductive age had menstrual cycle disorders.

Higher percentages of hypopituitarism may be detected biochemically in patients with clinically nonfunctioning adenomas. In a review of eight series of 1719 patients, 993 (58 percent) had laboratory evidence of pituitary hormone deficiency [14]. The most common pituitary hormone deficiencies were:

Growth hormone (GH) (87 percent, 220 of 252 tested). Testing for GH deficiency was less common in older series because GH deficiency was not thought to have important clinical consequences. (See "Growth hormone deficiency in adults".)

LH/FSH (hypogonadotropic hypogonadism; 1216 of 1699 patients tested, 72 percent).

Corticotropin (ACTH) (secondary adrenal insufficiency; 514 of 1699, 30 percent).

Thyroid-stimulating hormone (TSH) (central hypothyroidism; 402 of 1699, 24 percent).

Hormone excess

Gonadotroph adenomas — Although gonadotroph adenomas are considered to be "nonfunctioning," most do produce intact gonadotropins or their subunits. However, these adenomas are typically poorly differentiated and inefficient producers/secretors and do not raise serum gonadotropin concentrations. Thus, they are usually clinically "silent" and cannot be distinguished from other clinically nonfunctioning adenomas until immunohistochemistry is performed after pituitary surgery.

However, approximately 35 percent of gonadotroph adenomas secrete enough LH or FSH to raise serum gonadotropin levels [26], but clinical syndromes due to hypersecretion of intact gonadotropins are rare. However, several syndromes have been recognized (table 2) [27]:

Ovarian hyperstimulation has been reported in premenopausal women [28-34] and, rarely, in prepubertal girls [35,36]. The slight, but persistently, elevated serum FSH concentrations lead to recruitment of multiple dominant follicles, high serum estradiol (E2) concentrations (>500 pg/mL), and thickened endometrium on pelvic ultrasound (potentially suggestive of endometrial hyperplasia). The clinical picture is similar to ovarian stimulation with exogenous FSH when administered for fertility treatment (image 2).

Because the multiple follicles are not triggered to ovulate, women present with amenorrhea or oligomenorrhea [28-34], and prepubertal girls present with breast development, vaginal bleeding, and abdominal distension [35,36]. If pituitary surgery is successful in removing the adenoma but not removing the normal pituitary, gonadotropin secretion and ovarian function returns to normal [33,37-40].

An LH-secreting pituitary adenoma resulting in precocious puberty has been reported in two boys [41,42].

The majority of gonadotroph adenomas that secrete intact gonadotropins occur in middle-aged adults and do not result in a clinical syndrome. In postmenopausal women, for example, a gonadotroph adenoma that secretes intact gonadotropins would not result in a clinical syndrome, because gonadotropin levels are already high and a postmenopausal ovary cannot be stimulated to produce follicles or E2. However, in males, elevated serum testosterone concentration due to hypersecretion of intact LH and testicular enlargement due to FSH hypersecretion have been described [5,43,44].

Other pituitary adenomas

Somatotroph adenomas – In 100 consecutive patients with pituitary adenomas that were surgically excised, 24 had somatotroph adenomas by immunochemical staining [3]. Of these, eight (one-third) had an elevated insulin-like growth factor 1 (IGF-1) concentration but not even subtle manifestations of acromegaly and could therefore be considered to be clinically silent.

Corticotroph adenomas – Clinically silent corticotroph adenomas might be recognizable by higher plasma ACTH concentrations than other macroadenomas [4].

Elevated prolactin — Macroadenomas often compress the pituitary stalk and obstruct the normal inhibitory hypothalamic influence on the prolactin-producing cells, resulting in modestly elevated serum prolactin concentrations (usually <100 ng/mL but sometimes as high as 200 ng/mL). Illustrated in one study of 226 patients with nonfunctioning macroadenomas, a serum prolactin concentration >94 ng/mL reliably distinguished between lactotroph adenomas and nonfunctioning adenomas [45]. Rarely, gonadotroph adenomas cosecrete prolactin and gonadotropins.

Characteristic imaging features — As noted, gonadotroph adenomas are generally hormonally inefficient; as a result, by the time a gonadotroph adenoma produces supranormal serum concentrations of intact gonadotropins or their subunits, it is a macroadenoma (>1 cm) by imaging (image 1). MRI in a patient with neurologic symptoms usually shows a large intrasellar mass that is frequently extending outside of the sella. Elevation of the optic chiasm or extension into the cavernous sinuses or sphenoid sinus can also be detected. MRI with gadolinium is preferred to computed tomography (CT) because it provides superior resolution of the mass and its relation to surrounding structures. (See 'Pituitary imaging' below and "Causes, presentation, and evaluation of sellar masses", section on 'MRI'.)

Aggressive pituitary adenomas — Although most pituitary adenomas are benign and follow an indolent course, some are aggressive and partially or entirely resistant to all forms of treatment. A meta-analysis found that 31 percent of clinically silent corticotroph adenomas recurred, a similar frequency as other kinds of clinically silent adenomas. The management of some types of aggressive pituitary adenomas is discussed separately [46]. (See "Treatment of gonadotroph and other clinically nonfunctioning adenomas", section on 'Aggressive tumors'.)

EVALUATION

General approach — Our approach to the patient whose presenting signs, symptoms, or prior imaging suggests a sellar mass includes the following:

Take a detailed history and perform a physical examination, recognizing that any visual abnormalities or other neurologic symptoms could represent a sellar mass. The history should also focus on possible symptoms of hypopituitarism, including symptoms of hypogonadism in men (fatigue, decreased libido, erectile dysfunction) and women (amenorrhea/oligomenorrhea). (See 'Neurologic symptoms' above and 'Hormone deficiencies' above.)

Confirm the presence of a sellar mass by a magnetic resonance imaging (MRI) dedicated to this region, if not already done. If a sellar mass is confirmed, assess its size, relationship to chiasm, and cavernous sinuses.

Visual field and visual acuity testing. (See 'Visual field testing' below.)

Biochemical testing to detect other kinds of pituitary adenomas by their excessive hormonal secretion (eg, lactotroph, somatotroph, and, less commonly, corticotroph adenomas). (See 'Hormone excess' above.)

Biochemical testing for excessive secretion of gonadotropins and their subunits, as they are characteristic of gonadotroph adenomas. This includes measurement of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and alpha subunit concentrations. (See 'Hormone excess' above.)

Biochemical testing also for pituitary hypofunction due to compression of normal pituitary cells by the adenoma. (See 'Hormonal testing' below.)

We agree with the Endocrine Society Clinical Practice Guidelines on Pituitary Incidentaloma and suggest MRI, visual field testing, and biochemical evaluation for hormone hypersecretion and hypopituitarism for patients with pituitary incidentalomas that are >1 cm in size [47]. (See "Pituitary incidentalomas".)

Pituitary imaging — We suggest MRI for the initial imaging study for suspected adenomas because of its superior resolution and its ability to demonstrate the optic chiasm. MRI with gadolinium is preferred to computed tomography (CT) because it provides superior resolution of the mass and its relation to surrounding structures. MRI is also able to detect blood, thereby permitting recognition of hemorrhage into the pituitary and distinction of an aneurysm from other intrasellar lesions (image 1).

However, MRI will not distinguish adenomatous tissue from normal pituitary tissue. MRI will also not distinguish a gonadotroph adenoma from other pituitary macroadenomas and often not even from nonpituitary lesions. This topic is reviewed in more detail separately. (See "Causes, presentation, and evaluation of sellar masses", section on 'MRI'.)

Visual field testing — All patients with sellar masses >1 cm or elevating the optic chiasm, including those who deny visual symptoms, should undergo baseline Humphrey visual field testing and evaluation of visual acuity. A clinician experienced in evaluating visual field abnormalities, such as a neuro-ophthalmologist, should interpret the results.

Hormonal testing — Hypothalamic-pituitary hormonal function (both hyper- and hypofunction) should be evaluated whenever a large sellar mass (>1 cm) is seen on MRI to determine if it is a pituitary adenoma that can be recognized by hormonal hypersecretion.

Hypersecretion - The possibility of hormone excess should be evaluated to detect the presence of functioning pituitary adenomas. We therefore suggest measurements of:

Serum LH, FSH, and alpha subunit (gonadotroph adenoma). In countries where thyrotropin-releasing hormone (TRH) is available, the FSH and alpha subunit response to TRH will also identify a gonadotroph adenoma (table 2).

Serum prolactin (lactotroph adenomas).

Insulin-like growth factor 1 (IGF-1) (somatotroph adenomas).

Plasma ACTH, 24-hour urine free cortisol (corticotroph adenomas).

Hypopituitarism - Deficient secretion of other pituitary hormones often occurs due to the mass effect of the typically large gonadotroph adenomas and should always be investigated. Additional testing for hormone deficiencies due to compression of the normal pituitary tissue includes measurement of the serum concentrations of:

8 AM cortisol

Thyroxine (T4) (if elevated, measure thyroid-stimulating hormone [TSH] to evaluate the possibility of a thyrotroph adenoma)

Testosterone in men

Estradiol (E2) in women of premenopausal age with amenorrhea

The interpretation of pituitary tests and the diagnosis of hypopituitarism are discussed separately. (See "Diagnostic testing for hypopituitarism".)

Gonadotroph adenomas — In postmenopausal women, a sellar mass can be recognized as a gonadotroph adenoma biochemically by the combination of an elevated FSH and/or alpha subunit and a suppressed LH (table 2) [16].

Alpha subunit values should be interpreted in the context of normal values for the specific patient group and specific assay. The serum concentration of uncombined alpha subunit is elevated in women in three physiologic conditions [48-50]:

Menopause, in which the gonadotroph cells of the pituitary hypersecrete intact FSH and LH and uncombined alpha subunit

Pregnancy, in which the placenta secretes intact human chorionic gonadotropin (hCG) and uncombined alpha subunit

Ovarian stimulation with exogenous gonadotropins (hCG, human menopausal gonadotropins [hMG], FSH) for the treatment of infertility

In men, a sellar mass can be recognized as a gonadotroph adenoma by a supranormal basal serum FSH concentration (figure 1) [51]. An elevated concentration of alpha subunit indicates a gonadotroph adenoma, thyrotroph adenoma, or less differentiated glycoprotein adenoma. A supranormal response of intact FSH or alpha subunit to TRH also indicates a gonadotroph adenoma.

Finding evidence for a gonadotroph adenoma will not influence the choice of therapy (which is pituitary surgery), but recognizing that a sellar mass is a gonadotroph adenoma and not a nonpituitary lesion could influence the route of surgery and can be used as a tumor marker by which to evaluate the result of surgery and for subsequent monitoring. Finding evidence for one of the other types of clinically nonfunctioning adenomas could also open the possibility of pharmacologic treatment. (See "Treatment of gonadotroph and other clinically nonfunctioning adenomas".)

Somatotroph adenomas — Although somatotroph adenomas typically cause the characteristic clinical syndrome of acromegaly, some are silent. They can result in excessive hormonal secretion without even the subtlest clinical change ("clinically silent") or no clinical or biochemical evidence of excessive hormonal secretion ("totally silent"). In 100 consecutive patients with pituitary adenomas that were surgically excised, 24 had somatotroph adenomas by immunochemical staining [3]. Of these, eight (one-third) had an elevated IGF-1 concentration but not even subtle manifestations of acromegaly and could therefore be considered to be clinically silent.

Corticotroph adenomas — Corticotroph macroadenomas, unlike microadenomas, do not typically cause Cushing syndrome. However, they may be clinically silent and recognizable by elevated plasma corticotropin (ACTH) concentrations [4].

Lactotroph adenomas — Most lactotroph macroadenomas produce very high serum prolactin concentrations, but some are inefficient and do not. These may be difficult to distinguish from other sellar lesions that compress the pituitary stalk and obstruct the normal inhibitory hypothalamic influence on the prolactin producing cells, resulting in modestly elevated serum prolactin concentrations (usually <100 ng/mL but sometimes as high as 200 ng/mL). Illustrated in one study of 226 patients with nonfunctioning macroadenomas, a serum prolactin concentration >94 ng/mL reliably distinguished between lactotroph adenomas and nonfunctioning adenomas [45]. Rarely, gonadotroph adenomas cosecrete prolactin and gonadotropins.

DIAGNOSIS — A definitive diagnosis of a gonadotroph adenoma is made by pathologic evaluation of the excised tissue. Pituitary adenomas typically show effacement of the normal lobular pituitary architecture and instead show a monomorphic population of cells and loss of the normal reticulin pattern. Immunochemical staining may be positive for follicle-stimulating hormone (FSH)-beta, luteinizing hormone (LH)-beta, and/or alpha subunit. Even more likely is positive immunostaining for steroidogenic factor 1 (SF-1), the transcription factor responsible for the final differentiation of the gonadotroph cell [52].

However, the diagnosis of a gonadotroph adenoma can be made with a reasonable degree of certainty preoperatively in a patient with a large sellar mass in the following circumstances:

Serum prolactin concentration less than 100 ng/mL. (See 'Elevated prolactin' above.)

No symptoms or signs of acromegaly and serum concentration of insulin-like growth factor 1 (IGF-1) not elevated. (See "Causes and clinical manifestations of acromegaly" and "Diagnosis of acromegaly".)

No signs or symptoms of Cushing syndrome and 24-hour urine cortisol excretion not elevated. (See "Epidemiology and clinical manifestations of Cushing syndrome" and "Establishing the diagnosis of Cushing syndrome".)

In men, elevated basal serum concentrations of intact FSH and/or of alpha subunit (table 2). In countries where thyrotropin-releasing hormone (TRH) is available, an FSH response to TRH. Rarely, elevated LH and testosterone. Elevated FSH and LH and subnormal testosterone indicate primary hypogonadism. (See 'Primary hypogonadism' below.)

In premenopausal women, irregular menses, elevated FSH and estradiol (E2), low LH, and on pelvic ultrasound, massive polycystic ovaries and thickened endometrium.

In postmenopausal women, elevated FSH and/or alpha subunit and low LH (table 2). Elevation of both FSH and LH likely indicate only normal postmenopausal gonadotropin secretion.

DIFFERENTIAL DIAGNOSIS — Pituitary adenomas are the most common cause of a large sellar mass, but other causes include craniopharyngioma, meningioma, malignant tumors, Rathke's cleft cysts, and hypophysitis. Any sellar masses >1 cm may present with neurologic symptoms similar to clinically nonfunctioning pituitary adenomas. Evaluation of a large sellar mass includes imaging with magnetic resonance imaging (MRI), and hormonal evaluation for pituitary hyper- and hypofunction. (See "Causes, presentation, and evaluation of sellar masses", section on 'Evaluation of a sellar mass' and "Pituitary incidentalomas", section on 'Lesions 10 mm or larger'.)

Lactotroph macroadenoma — As noted above, a large sellar mass associated with a prolactin concentration <100 ng/mL probably does not represent a lactotroph adenoma. Large sellar masses compress the pituitary stalk and thereby prevent dopamine from the hypothalamus from reaching the pituitary, thus decreasing normal inhibition of prolactin secretion. The result is a mild elevation of serum prolactin (>20 ng/mL [eg, higher than normal] but usually <100 ng/mL) [45,53]. (See 'Elevated prolactin' above and "Clinical manifestations and evaluation of hyperprolactinemia".)

Primary hypogonadism — Longstanding primary hypogonadism can cause gonadotroph cell hypertrophy and therefore overall pituitary enlargement [54,55] and, in this way, as well as in elevated gonadotropin concentrations, is similar to gonadotroph adenomas. Primary hypogonadism differs from gonadotroph adenomas in several ways:

The degree of pituitary enlargement is much less

Both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are elevated

Neither intact gonadotropins nor their subunits respond to thyrotropin-releasing hormone (TRH) [51,56]

Polycystic ovary syndrome — Women with polycystic ovary syndrome (PCOS) have multiple follicles on pelvic ultrasound. However, they are small and arranged in a peripheral pattern, unlike the follicles described in the cases of ovarian hyperstimulation syndrome in women with gonadotroph adenomas (image 2) [28-34]. In addition, serum FSH concentrations are low in PCOS, not normal or high as they would be with a gonadotroph adenoma. Lastly, a serum estradiol (E2) concentration >500 pg/mL should strongly raise the suspicion that the multiple ovarian cysts are due to a gonadotroph adenoma (image 2) rather than PCOS.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pituitary tumors and hypopituitarism".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Pituitary adenoma (The Basics)")

SUMMARY

Prevalence of nonfunctioning adenomas – Approximately 25 to 35 percent of all pituitary adenomas are clinically nonfunctioning or "silent"; 70 to 90 percent of these are gonadotroph adenomas. (See 'Overview of pituitary adenomas' above.)

Clinical presentation – Clinically nonfunctioning adenomas (including gonadotroph adenomas) usually come to clinical attention when they become large enough to cause neurologic symptoms such as impaired vision (diminished vision in the temporal fields [bitemporal hemianopsia] and diminished visual acuity), and nonspecific headaches, (See 'Neurologic symptoms' above.)

Some are detected as an incidental finding when magnetic resonance imaging (MRI) is done for other reasons. (See 'Incidental finding on imaging' above.)

Approximately 60 percent of patients at the time of diagnosis have hypopituitarism due to compression by the macroadenoma. Hormonal deficiencies are usually not the presenting symptoms. (See 'Symptoms due to hormonal abnormalities' above.)

Gonadotroph adenomas are difficult to recognize because they secrete variably and inefficiently, and often do not cause a clinical syndrome. (See 'Hormone excess' above.)

Evaluation – Evaluation of the patient who presents with neurologic symptoms suggestive of a clinically nonfunctioning sellar mass should first include pituitary MRI. If a sellar mass >1 cm is detected on pituitary MRI, the following should be performed (see 'Evaluation' above):

Visual field testing

Biochemical testing for hypersecretion of other pituitary hormones (serum prolactin, insulin-like growth factor 1 [IGF-1], and 24-hour urine free cortisol) (see 'Hormone excess' above)

Biochemical testing for gonadotropins and their subunit (follicle-stimulating hormone [FSH], luteinizing hormone [LH] and alpha subunit)

Testing for hypopituitarism – 8 AM cortisol, thyroxine (T4), testosterone in men and estradiol (E2) in women of premenopausal age (see 'Hormonal testing' above)

Diagnosis The diagnosis of a gonadotroph adenoma is likely if there is a large sellar mass, no clinical or biochemical evidence of acromegaly or Cushing syndrome, the serum prolactin is <100 ng/mL, and the concentrations of gonadotropins are characteristic (table 2). (See 'Diagnosis' above.)

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Topic 6627 Version 26.0

References

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